UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO SECTION 13a-16 OR 15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the month of November,
Commission File Number: 001-36815
(Exact Name of Registrant as Specified in Its Charter)
Tuborg Boulevard 12
DK-2900 Hellerup
Denmark
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐
INCORPORATION BY REFERENCE
This report on Form 6-K shall be deemed to be incorporated by reference into the registration statements on Form S-8 (Registration Numbers 333-228576, 333-203040, 333-210810, 333-211512, 333-213412, 333-214843, 333-216883, 333-254101, 333-261550, 333-270088, 333-277519, and 333-281916) and Form F-3 (Registration Numbers 333-209336 and 333-282196) of Ascendis Pharma A/S (the “Company”) (including any prospectuses forming a part of such registration statements) and to be a part thereof from the date on which this report is filed, to the extent not superseded by documents or reports subsequently filed or furnished.
Information Contained in this Report on Form 6-K
Financial Statements
This report contains the Company’s Unaudited Condensed Consolidated Interim Financial Statements as of and for the period ended September 30, 2024, including Management’s Discussion and Analysis of Financial Condition and Results of Operations for the period presented therein.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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Ascendis Pharma A/S |
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Date: November 14, 2024 |
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By: |
/s/ Michael Wolff Jensen |
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Michael Wolff Jensen |
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Executive Vice President, Chief Legal Officer |
TABLE OF CONTENTS
1. |
Unaudited Condensed Consolidated Interim Financial Statements – September 30, 2024 |
F-1 |
2. |
Management’s Discussion and Analysis of Financial Condition and Results of Operations |
1 |
ASCENDIS PHARMA A/S
INDEX TO UNAUDITED CONDENSED CONSOLIDATED INTERIM FINANCIAL STATEMENTS
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Page |
F-2 |
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F-3 |
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F-4 |
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F-5 |
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Notes to the Unaudited Condensed Consolidated Interim Financial Statements |
F-6 |
F-1
Unaudited Condensed Consolidated Interim Statements of Profit or (Loss)
and Other Comprehensive Income or (Loss) for the Three and Nine Months Ended September 30, 2024 and 2023
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Three Months Ended |
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Nine Months Ended |
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Notes |
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2024 |
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2023 |
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2024 |
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2023 |
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(EUR’000) |
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(EUR’000) |
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Consolidated Statement of Profit or (Loss) |
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Revenue |
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5 |
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Cost of sales |
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Gross profit |
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Research and development costs |
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Selling, general, and administrative expenses |
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Operating profit/(loss) |
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( |
) |
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( |
) |
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( |
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( |
) |
Share of profit/(loss) of associates |
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( |
) |
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( |
) |
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( |
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( |
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Finance income |
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Finance expenses |
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Profit/(loss) before tax |
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( |
) |
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( |
) |
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( |
) |
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( |
) |
Income taxes/(expenses) |
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( |
) |
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( |
) |
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( |
) |
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( |
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Net profit/(loss) for the period |
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( |
) |
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( |
) |
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( |
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( |
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Attributable to owners of the Company |
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( |
) |
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( |
) |
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( |
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( |
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Basic and diluted earnings/(loss) per share |
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€ |
( |
) |
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€ |
( |
) |
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€ |
( |
) |
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€ |
( |
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Number of shares used for calculation (basic and diluted) (1) |
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(EUR’000) |
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(EUR’000) |
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Consolidated Statement of Comprehensive Income or (Loss) |
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Net profit/(loss) for the period |
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( |
) |
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( |
) |
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( |
) |
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( |
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Other comprehensive income/(loss) |
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Items that may be reclassified subsequently to profit or (loss): |
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Exchange differences on translating foreign operations |
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( |
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Other comprehensive income/(loss) for the period, net of tax |
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( |
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Total comprehensive income/(loss) for the period, net of tax |
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( |
) |
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( |
) |
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( |
) |
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( |
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Attributable to owners of the Company |
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( |
) |
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( |
) |
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( |
) |
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( |
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F-2
Unaudited Condensed Consolidated Interim Statements of Financial Position
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Notes |
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September 30, |
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December 31, |
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(EUR’000) |
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Assets |
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Non-current assets |
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Intangible assets |
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Property, plant and equipment |
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Investment in associates |
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4 |
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Other receivables |
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10 |
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Current assets |
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Inventories |
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Trade receivables |
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10 |
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Income tax receivables |
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Other receivables |
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10 |
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Prepayments |
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Marketable securities |
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10 |
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Cash and cash equivalents |
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10 |
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Total assets |
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Equity and liabilities |
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Equity |
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Share capital |
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8 |
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Distributable equity |
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( |
) |
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( |
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Total equity |
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4 |
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( |
) |
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( |
) |
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Non-current liabilities |
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Borrowings |
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2, 10 |
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Contract liabilities |
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Deferred tax liabilities |
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Current liabilities |
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Convertible notes, matures in April 2028 |
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Borrowings |
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2, 10 |
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Derivative liabilities |
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2, 10 |
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Other current liabilities |
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Borrowings |
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2, 10 |
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Contract liabilities |
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Trade payables and accrued expenses |
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10 |
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Other liabilities |
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10 |
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Income tax payables |
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Provisions |
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Total liabilities |
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Total equity and liabilities |
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F-3
Unaudited Condensed Consolidated Interim Statements of Changes in Equity
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Distributable Equity |
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Share |
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Share |
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Treasury |
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Foreign |
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Accumulated |
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Total |
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(EUR’000) |
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Equity at January 1, 2024 |
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( |
) |
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( |
) |
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( |
) |
|||
Net profit/(loss) for the period |
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— |
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— |
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— |
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— |
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( |
) |
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( |
) |
Other comprehensive income/(loss), net of tax |
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— |
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— |
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— |
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— |
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Total comprehensive income/(loss) |
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— |
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— |
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— |
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( |
) |
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( |
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Transactions with Owners |
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Share-based payment (Note 7) |
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— |
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— |
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— |
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— |
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Transfer under stock incentive programs |
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— |
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— |
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— |
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( |
) |
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— |
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Capital increase |
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— |
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— |
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— |
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Cost of capital increase |
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— |
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( |
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— |
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— |
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— |
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( |
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Equity at September 30, 2024 |
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( |
) |
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( |
) |
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( |
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Distributable Equity |
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Share |
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Share |
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Treasury |
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Foreign |
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Accumulated |
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Total |
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(EUR’000) |
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Equity at January 1, 2023 |
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( |
) |
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( |
) |
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Net profit/(loss) for the period |
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— |
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— |
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— |
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— |
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( |
) |
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( |
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Other comprehensive income/(loss), net of tax |
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— |
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— |
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— |
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( |
) |
|
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— |
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( |
) |
Total comprehensive income/(loss) |
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— |
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— |
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— |
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( |
) |
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( |
) |
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( |
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Transactions with Owners |
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Share-based payment (Note 7) |
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— |
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— |
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— |
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— |
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Capital increase |
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— |
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— |
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— |
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Equity at September 30, 2023 |
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( |
) |
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( |
) |
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( |
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F-4
Unaudited Condensed Consolidated Interim Cash Flow Statements for the
Nine Months Ended September 30, 2024 and 2023
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Nine Months Ended |
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2024 |
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2023 |
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(EUR’000) |
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Operating activities |
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Net profit/(loss) for the period |
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( |
) |
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( |
) |
Reversal of finance income |
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( |
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( |
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Reversal of finance expenses |
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Reversal of (gain)/loss on disposal of property, plant and equipment |
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( |
) |
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— |
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Reversal of income taxes (expenses) |
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Adjustments for non-cash items: |
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Non-cash consideration relating to revenue |
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( |
) |
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( |
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Share of profit/(loss) of associates |
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Share-based payment |
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Depreciation |
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Amortization |
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Changes in working capital: |
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Inventories |
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( |
) |
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( |
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Receivables |
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( |
) |
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Prepayments |
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( |
) |
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Contract liabilities (deferred income) |
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( |
) |
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( |
) |
Trade payables, accrued expenses and other payables |
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( |
) |
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Increase/(decrease) in provisions |
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Cash flows generated from/(used in) operations |
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( |
) |
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( |
) |
Finance income received |
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Finance expenses paid |
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( |
) |
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( |
) |
Income taxes received/(paid) |
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( |
) |
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( |
) |
Cash flows from/(used in) operating activities |
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( |
) |
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( |
) |
Investing activities |
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Acquisition of property, plant and equipment |
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( |
) |
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( |
) |
Proceeds from disposal of property, plant and equipment |
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Development expenditures (software) |
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( |
) |
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— |
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Settlement of marketable securities |
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Cash flows from/(used in) investing activities |
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Financing activities |
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Repayment of borrowings |
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( |
) |
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( |
) |
Net proceeds from borrowings |
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Proceeds from exercise of warrants |
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Net proceeds from follow-on public offerings |
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— |
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Cash flows from/(used in) financing activities |
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Increase/(decrease) in cash and cash equivalents |
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( |
) |
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Cash and cash equivalents at January 1 |
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Effect of exchange rate changes on balances held in foreign currencies |
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Cash and cash equivalents at September 30 |
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Cash and cash equivalents include: |
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Bank deposits |
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Cash and cash equivalents at September 30 |
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F-5
Notes to the Unaudited Condensed Consolidated Interim Financial Statements
Note 1—General Information
Ascendis Pharma A/S, together with its subsidiaries, is applying its innovative TransCon technology platform to build a leading, fully integrated, global biopharma company focused on making a meaningful difference in patients’ lives. Ascendis Pharma A/S was incorporated in 2006 and is headquartered in Hellerup, Denmark. Unless the context otherwise requires, references to the “Company,” “we,” “us,” and “our,” refer to Ascendis Pharma A/S and its subsidiaries.
The address of the Company’s registered office is Tuborg Boulevard 12, DK-2900, Hellerup, Denmark.
On February 2, 2015, the Company completed an initial public offering which resulted in the listing of American Depositary Shares (“ADSs”), representing the Company’s ordinary shares, under the symbol “ASND” in the United States on the Nasdaq Global Select Market.
The Company’s Board of Directors (the “Board”) approved these unaudited condensed consolidated interim financial statements on November 14, 2024.
Note 2—Summary of Material Accounting Policies
Basis of Preparation
The unaudited condensed consolidated interim financial statements of the Company are prepared in accordance with International Accounting Standard 34, “Interim Financial Reporting.” Certain information and disclosures normally included in the annual consolidated financial statements prepared in accordance with IFRS Accounting Standards (“IFRS”) have been condensed or omitted. Accordingly, these unaudited condensed consolidated interim financial statements should be read in conjunction with the Company’s audited annual consolidated financial statements for the year ended December 31, 2023 and accompanying notes, which have been prepared in accordance with IFRS as issued by the International Accounting Standards Board (the “IASB”) and as adopted by the European Union (the “EU”).
The accounting policies applied are consistent with those of the previous financial year. A description of the accounting policies is provided in the Accounting Policies section of the audited consolidated financial statements as of and for the year ended December 31, 2023.
New and Amended IFRS Accounting Standards and Interpretations
The Company has applied amendments to paragraphs 69 to 76 of IAS 1, “Presentation of Financial Statements,” which was effective for annual reporting periods beginning on or after January 1, 2024 and must be applied retrospectively. The amendments to IAS 1 specify the requirements for classifying liabilities as current or non-current. The amendments clarify:
The convertible senior notes (“convertible notes”) include an embedded equity conversion option which is not deemed closely related to the financial liability and was initially recognized and measured separately at fair value as derivative liabilities based on the stated terms upon issuance of the convertible notes. The conversion option is classified as a foreign currency conversion option and thus not convertible into a fixed number of shares for a fixed amount of cash. Accordingly, the conversion option is subsequently recognized and measured as a derivative liability at fair value through profit or loss, with any subsequent remeasurement gains or losses recognized as part of finance income or expenses.
F-6
Since the embedded derivative is not an equity instrument under IFRS, the amendments require the convertible notes (presented as part of borrowings in the statement of financial position) and derivative liabilities, presented as non-current liabilities at December 31, 2023, to be presented as current liabilities. The amendments require presentation of the convertible notes as current liabilities even though: the initial conversion price of $
On December 31, 2023, lease liabilities were presented separately in the consolidated statements of financial position. At December 31, 2023, carrying amount of lease liabilities was €
Accordingly, since March 31, 2024, borrowings comprise convertible notes, royalty funding liabilities, and lease liabilities. The change to presentation had no other impact on the unaudited condensed consolidated financial statements.
The applied amendments had no other impact on the unaudited condensed consolidated interim financial statements.
Other amendments apply for the first time in 2024, but do not have an impact on the unaudited condensed consolidated interim financial statements.
New IFRS Accounting Standards Not Yet Effective
The IASB has issued a number of new or amended standards, which have not yet become effective or have not yet been adopted by the EU. Therefore, these new standards have not been incorporated in these unaudited condensed consolidated interim financial statements.
IFRS 18, “Presentation and Disclosure in Financial Statements”
In April 2024, the IASB issued IFRS 18, “Presentation and Disclosure in Financial Statements” (“IFRS 18”), which replaces IAS 1, “Presentation in Financial Statements.” IFRS 18 introduces new categories and subtotals in the statement of profit or loss, into:
In addition, IFRS 18 includes new requirements for the location, aggregation and disaggregation of financial information, and disclosure of management-defined performance measures, as defined, if any. IFRS 18 does not include any measurement changes.
If approved by the EU, the amendments will be effective for annual reporting periods beginning on or after January 1, 2027, and must be applied retrospectively, with early adoption permitted. While IFRS 18 will change the structure and subtotal in the statement of profit or loss, the full impact from implementing IFRS 18 is currently being analyzed by the Company.
The consolidated financial statements are not expected to be affected by other new or amended standards.
F-7
Note 3—Significant Accounting Judgements and Estimates
In the application of the Company’s accounting policies, management is required to make judgements, estimates and assumptions about the carrying amounts of assets and liabilities that are not readily apparent from other sources. Judgements, estimates and assumptions applied are based on historical experience and other factors that are relevant, and which are available at the reporting date. Uncertainty concerning estimates and assumptions could result in outcomes that require a material adjustment to assets and liabilities in future periods.
The unaudited condensed consolidated interim financial statements do not include all disclosures for significant accounting judgements, estimates and assumptions, that are required in the annual consolidated financial statements, and therefore should be read in conjunction with the Company’s audited consolidated financial statements as of and for the year ended December 31, 2023.
Estimates and underlying assumptions are reviewed on an ongoing basis. Revisions to accounting estimates are recognized prospectively. While the application of critical accounting estimates is subject to material estimation uncertainties, management’s ongoing revisions of critical accounting estimates and underlying assumptions have, except for revenue and provisions, as described below, not revealed any material impact in any of the periods presented in the unaudited condensed consolidated interim financial statements.
There have been no other changes to the application of significant accounting judgements, or estimation uncertainties regarding accounting estimates compared to December 31, 2023.
Revenue and Provisions - Change in Accounting Estimates
Revenue includes provision for a variety of sales deductions such as prompt pay discounts, shelf stock adjustments and applicable sales rebates attributable to various commercial arrangements, managed healthcare organizations, government programs, and co-pay arrangement. Provisions for sales deductions attributed to commercial arrangements are recognized when the related sales take place and measured using the expected value method. Payable amounts for commercial arrangements are generally settled within 90-180 days from the transaction date. Provisions for unsettled sales deductions under commercial arrangements are estimated on the basis of a percentage of sales as defined by individual agreements and contracts. Further inputs to the calculations are based on payer channel mix, current contract prices under eligible programs and current inventory levels in the distribution channels. Inputs to the calculations are subject to estimation and assumptions and are based on historical experience and other factors that are relevant, and which are available at the reporting date. These estimates and assumptions are subject to material uncertainties and could result in outcomes that require a material adjustment in future periods.
Revenue from for the nine months ended September 30, 2024 was negatively impacted by an adjustment to estimates and assumptions for sales deductions of €
Total provisions for the year ended, December 31, 2023 and nine months ended September 30, 2024, were €
Note 4—Significant Events in the Reporting Period
Completion of Follow-On Public Offering
On September 19, 2024, the Company entered into an underwriting agreement (the “Underwriting Agreement”) with J.P. Morgan Securities LLC, Morgan Stanley & Co. LLC, Evercore Group L.L.C. and Goldman Sachs & Co. LLC, as representatives of the several underwriters named therein (collectively, the “Underwriters”), pursuant to which the Company agreed to issue and sell
On September 23, 2024, the Offering closed and the Company completed the sale and issuance of an aggregate of
F-8
Royalty Funding Liabilities
In September, 2024, the Company entered into a $
Eyconis, Inc.
In January 2024, the Company announced the formation and launch with Frazier Life Sciences of Eyconis, Inc. (“Eyconis”), a separate company created to develop, manufacture, and commercialize TransCon ophthalmology assets globally, together with a $
The Company has granted Eyconis exclusive rights to develop and commercialize TransCon ophthalmology products globally and received an equity position in the newly formed company. As consideration for the granting of such rights, the Company received, as consideration, approximately
Equity Development
As of September 30, 2024, the unaudited condensed consolidated interim statements of financial position presented a negative balance of equity of €
Based on its current operating plan, the Company believes that the existing capital resources as of September 30, 2024, will be sufficient to meet projected cash requirements for at least twelve months from the date of this report. However, the Company's operating plan may change as a result of many factors that are currently unknown, and the Company may need to seek additional funds sooner than planned. Further details regarding borrowings including maturity analysis are provided in Note 10, “Financial Assets and Liabilities.”
F-9
Note 5—Revenue
Revenue has been recognized in the unaudited condensed consolidated interim statements of profit or loss in the following amounts:
|
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Three Months Ended |
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Nine Months Ended |
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2024 |
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2023 |
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2024 |
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2023 |
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(EUR’000) |
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(EUR’000) |
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||||||||||
Revenue |
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Commercial products |
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Rendering of services |
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Clinical supply |
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— |
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Licenses |
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Total revenue |
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Attributable to |
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Commercial customers |
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Collaboration partners and license agreements |
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Total revenue |
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Specified by timing of recognition |
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Recognized over time |
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Recognized at a point in time |
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Total revenue |
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Specified per geographical area |
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Europe |
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North America |
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170,833 |
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Rest of world |
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Total revenue |
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Commercial Customers
Revenue to commercial customers primarily relates to sale of SKYTROFA® (lonapegsomatropin-tcgd) and primarily in the U.S. market, which is sold to specialty pharmacies and specialty distributors. In addition, the Company began shipping SKYTROFA to customers in Germany in September 2023. In November 2023, TransCon PTH received regulatory approval in the EU and European Economic Area countries and is marketed as YORVIPATH® (palopegteriparatide). In August 2024, TransCon PTH received regulatory approval in the U.S. and will be marketed in the U.S. as YORVIPATH. The Company began shipping YORVIPATH to customers in Europe in the first quarter of 2024.
For the three and nine months ended September 30, 2024, revenue from SKYTROFA were €
For the three and nine months ended September 30, 2024 and 2023,
Collaboration Partners and License Agreements
Revenue attributable to collaboration partners and license agreements relates to Eyconis, Teijin Limited and VISEN Pharmaceuticals. Under the collaboration agreements, the Company provides various research and development services which are invoiced to collaboration partners. Revenue for these activities is presented as part of “Rendering of services.” Employment costs related to these activities are presented as Research and Development Costs in the consolidated statement of profit or loss.
Eyconis, Inc.
On January 29, 2024, the Company announced the formation and launch with Frazier Life Sciences of Eyconis, Inc., a separate company created to develop, manufacture, and commercialize TransCon ophthalmology assets globally, together with a $
The Company has granted Eyconis exclusive rights to develop and commercialize TransCon ophthalmology products globally and received, as consideration, an equity position in the newly formed company. In addition, the Company is eligible to receive development, regulatory, and sales milestone payments, plus single digit royalties on global net sales of commercialized products, if any.
F-10
The Company is expected to provide various research and development services, which are subject to separate remuneration, and which will be recognized as revenue over time as rendering of services or reimbursement revenue, as applicable.
For the nine months ended September 30, 2024, revenue from “Licenses” of €
For the nine months ended September 30, 2024,
Teijin Limited
On November 29, 2023, the Company entered into an exclusive license agreement with Teijin Limited (the “Teijin Agreement”) for the further development and commercialization of TransCon hGH, TransCon PTH, and TransCon CNP for endocrinology rare disease (the “Licensed Products”) in Japan. Under the terms of the Teijin Agreement, the Company received an upfront payment of $
Further, the Company will provide clinical and commercial supply, and development services for joint activities, which are subject to separate remuneration, and which will be recognized as revenue over time as rendering of services or reimbursement revenue, as applicable.
At September 30, 2024, none of the Licensed Products have received marketing authorization in Japan. The Licensed Products are patent protected, where future activities do not affect their existing stand-alone functionalities. Accordingly, all three licenses have been classified as “right-to-use” licenses, with revenue recognized at a point in time, where the licensee is granted access to the IP.
Development and regulatory milestones of up to $
For the nine months ended September 30, 2024,
VISEN Pharmaceuticals
Revenue from collaboration partners and license agreements also includes license income, rendering of services and sale of clinical supply under three licenses agreements with VISEN Pharmaceuticals, which were entered into in 2018.
Note 6—Segment Information
The Company is managed and operated as
Note 7—Share-Based Payment
As an incentive to the senior management, other employees, members of the Board and select consultants, Ascendis Pharma A/S has established warrant programs, a Restricted Stock Unit (“RSU”) program adopted in December 2021, and a Performance Stock Unit (“PSU”) program adopted in February 2023, which are all classified as equity-settled share-based payment transactions.
Share-Based Compensation Costs
Share-based compensation costs are determined using the grant date fair value and are recognized over the vesting period as research and development costs, selling, general and administrative expenses, or cost of sales. For the three and nine months ended September 30, 2024 and 2023, share-based compensation costs recognized in the unaudited condensed consolidated interim statement of profit or loss were €
F-11
Restricted Stock Unit Program
RSUs are granted by the Board to members of senior management, certain other employees and certain members of the Board (the “RSU-holders”). Further, RSUs may be granted to select consultants.
One RSU represents a right for the RSU-holder to receive one ADS representing ordinary shares of Ascendis Pharma A/S upon vesting, if the vesting conditions are met. RSUs granted vest over three years with 1/3 of the RSUs vesting on each anniversary date from the date of grant, and require RSU-holders to be employed, appointed as member of the Board, or retained as a consultant (the “service conditions”).
Performance Stock Unit Program
PSUs are granted by the Board to certain members of senior management (the “PSU-holders”). In addition, PSUs may be granted to other employees, select consultants and members of the Board.
One PSU represents a right for the PSU-holder to receive one ADS representing ordinary shares of Ascendis Pharma A/S upon vesting. PSUs vest in a manner similar to the service conditions of the RSUs. For the March 2023 PSU grant, in addition to service conditions, vesting is also contingent upon achievement of performance-based targets as determined by the Board, provided that no more than 10% of each tranche may be directly attributable to accomplishment of financial results achieved in the financial year prior to the vesting date.
RSUs and PSUs generally cease to vest from the date of termination of employment or Board membership, as applicable, whereas unvested RSUs or PSUs will forfeit. The Board may at its discretion and on an individual basis decide to deviate from the vesting conditions, including deciding to accelerate vesting in the event of termination of employment or Board membership, as applicable.
All RSUs and PSUs are expected to be settled at the time of vesting by treasury shares that are ADSs repurchased by the Company. The Company may at its sole discretion choose to make a cash settlement instead of delivering ADSs.
RSU and PSU Activity
The following table specifies the number of RSUs and PSUs granted and outstanding at September 30, 2024:
|
|
Restricted Stock Units |
|
|
Performance Stock Units |
|
|
Total |
|
|||
Outstanding |
|
(Number) |
|
|||||||||
January 1, 2024 |
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|
|
|
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|
|||
Granted during the period |
|
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|
|||
Transferred during the period |
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
Forfeited during the period |
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
September 30, 2024 |
|
|
|
|
|
|
|
|
|
|||
Specified by vesting year |
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|
|||
2024 |
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|
|||
2025 |
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|
|||
2026 |
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|
|||
2027 |
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|
|||
September 30, 2024 |
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|
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|
|||
Warrant Program
Warrants are granted by the Board in accordance with authorizations given to it by the shareholders of Ascendis Pharma A/S to all employees, members of the Board and select consultants. Each warrant carries the right to subscribe for one ordinary share of a nominal value of DKK
F-12
Warrant Activity
The following table specifies the warrant activity for the nine months ended September 30, 2024:
|
|
Total |
|
|
Weighted |
|
||
|
|
(Number) |
|
|
(EUR) |
|
||
Outstanding |
|
|
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|
|
|
||
January 1, 2024 |
|
|
|
|
|
|
||
Granted during the period |
|
|
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|
|
|
||
Exercised during the period |
|
|
( |
) |
|
|
|
|
Forfeited during the period |
|
|
( |
) |
|
|
|
|
September 30, 2024 |
|
|
|
|
|
|
||
Vested at September 30, 2024 |
|
|
|
|
|
|
||
The exercise prices of outstanding warrants under the Company’s warrant programs range from €
Note 8—Share Capital
The share capital of Ascendis Pharma A/S consists of
Note 9—Treasury Shares
The development in the holding of treasury shares is as follows:
|
|
Nominal |
|
|
Holding |
|
|
Holding in |
|
|||
|
|
(EUR’000) |
|
|
(Number) |
|
|
|
|
|||
Treasury shares |
|
|
|
|
|
|
|
|
|
|||
January 1, 2024 |
|
|
|
|
|
|
|
|
% |
|||
Transferred under stock incentive programs |
|
|
( |
) |
|
|
( |
) |
|
|
|
|
September 30, 2024 |
|
|
|
|
|
|
|
|
% |
|||
F-13
Note 10—Financial Assets and Liabilities
The following table specifies financial assets and liabilities:
|
|
September 30, |
|
|
December 31, |
|
||
|
|
(EUR’000) |
|
|||||
Financial assets by category |
|
|
|
|
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|
||
Trade receivables |
|
|
|
|
|
|
||
Other receivables (excluding income tax and indirect tax receivables) |
|
|
|
|
|
|
||
Marketable securities |
|
|
— |
|
|
|
|
|
Cash and cash equivalents |
|
|
|
|
|
|
||
Financial assets measured at amortized cost |
|
|
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||
Total financial assets |
|
|
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|
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|
||
Classified in the statement of financial position |
|
|
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|
|
||
Non-current assets |
|
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|
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|
||
Current assets |
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|
||
Total financial assets |
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||
|
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|
||
Financial liabilities by category |
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||
Borrowings |
|
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|
|
|
||
Convertible senior notes |
|
|
|
|
|
|
||
Royalty funding liabilities |
|
|
|
|
|
|
||
Lease liabilities |
|
|
|
|
|
|
||
Trade payables and accrued expenses |
|
|
|
|
|
|
||
Other liabilities (excluding income tax, indirect tax, and employee related payables) |
|
|
|
|
|
— |
|
|
Financial liabilities measured at amortized cost |
|
|
|
|
|
|
||
Derivative liabilities |
|
|
|
|
|
|
||
Financial liabilities measured at fair value through profit or loss |
|
|
|
|
|
|
||
Total financial liabilities |
|
|
|
|
|
|
||
Classified in the statement of financial position |
|
|
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|
|
|
||
Non-current liabilities |
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|
|
|
||
Current liabilities |
|
|
|
|
|
|
||
Total financial liabilities |
|
|
|
|
|
|
||
Convertible Senior Notes
In March 2022, the Company issued an aggregate principal amount of $
The convertible notes accrue interest at a rate of
The convertible notes will be optionally redeemable, in whole or in part (subject to certain limitations), at the Company’s option at any time, and from time to time, on or after
On September 30, 2024, the carrying amount of the convertible notes was €
F-14
Royalty Funding Liabilities
The Company has entered into capped synthetic royalty funding agreements with Royalty Pharma (the “Purchaser”), which is presented as royalty funding liabilities, and represents the Company’s contractual obligations to pay a predetermined percentage of future commercial revenue until reaching a predetermined multiple of proceeds received, according to the detailed provisions of the synthetic royalty funding agreements.
On September 30, 2024, the carrying amount of the royalty funding liabilities was €
YORVIPATH Agreement
In September 2024, the Company entered into a $
Under the terms of the Royalty Pharma Yorvipath Agreement, the Company received an upfront payment of $
The Royalty Pharma Yorvipath Agreement includes a buy-out option, which provides the Company with the right to settle all outstanding liabilities at any time by paying a buy-out amount equal to
SKYTROFA Agreement
In September 2023, the Company entered into a $
Under the terms of the Royalty Pharma Skytrofa Agreement, the Company received an upfront payment of $
The Royalty Pharma Skytrofa Agreement includes a buy-out option, which provides the Company with the right to settle all outstanding liabilities at any time by paying a buy-out amount equal to
Derivative Liabilities
Derivative liabilities relate to the foreign currency conversion option embedded in the convertible notes.
Fair value cannot be measured based on quoted prices in active markets or other observable inputs, and accordingly, derivative liabilities are measured by using the Black-Scholes option pricing model. Fair value of the option is calculated, applying the following assumptions: (1) conversion price; (2) the Company’s share price; (3) maturity of the option; (4) a risk-free interest rate equaling the effective interest rate on a U.S. government bond with the same lifetime as the maturity of the option; (5) no payment of dividends; and (6) an expected volatility using the Company’s share price (
For additional description of fair values, refer to the following section “Fair Value Measurement.”
F-15
Sensitivity Analysis
On September 30, 2024, all other inputs and assumptions held constant, a
Similarly, on September 30, 2024, all other inputs and assumptions held constant, a
Fair Value Measurement
Because of the short-term maturity for cash and cash equivalents, receivables and trade payables, their fair value approximate carrying amount. Fair value of lease liabilities are not disclosed. Fair value compared to carrying amount of marketable securities, convertible notes, royalty funding liabilities and derivative liabilities, and their level in the fair value hierarchy is summarized in the following table, where:
Level 1 is quoted prices (unadjusted) in active markets for identical assets or liabilities that the entity can access at the measurement date;
Level 2 is based on valuation techniques for which the lowest level input that is significant to the fair value measurement is directly or indirectly observable;
Level 3 is based on valuation techniques for which the lowest level input that is significant to the fair value measurement is unobservable.
|
|
September 30, 2024 |
|
December 31, 2023 |
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|
||||
|
|
Carrying |
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Fair value |
|
Carrying |
|
Fair value |
|
Fair value level |
|
|
(EUR’000) |
|
(1-3) |
||||||
Financial assets |
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|
|
|
|
Marketable securities |
|
— |
|
— |
|
|
|
1 |
||
Financial assets measured at amortized cost |
|
— |
|
— |
|
|
|
|
||
Financial liabilities |
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|
|
|
|
|
|
|
|
Convertible senior notes |
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|
|
|
|
3 |
||||
Royalty funding liabilities |
|
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|
3 |
||||
Financial liabilities measured at amortized cost |
|
|
|
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|
||||
Derivative liabilities |
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|
|
|
|
3 |
||||
Financial liabilities measured at fair value through profit or loss |
|
|
|
|
|
|
||||
The following table specifies movements in level 3 fair value measurements:
|
|
2024 |
|
|
2023 |
|
||
|
|
(EUR’000) |
|
|||||
Derivative liabilities |
|
|
|
|
|
|
||
January 1 |
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|
|
|
|
|
||
Remeasurement recognized in finance (income) or expense |
|
|
|
|
|
( |
) |
|
September 30 |
|
|
|
|
|
|
||
F-16
Maturity Analysis
|
|
< 1 year |
|
|
1-5 years |
|
|
>5 years |
|
|
Total |
|
|
Carrying |
|
|||||
|
|
(EUR’000) |
|
|||||||||||||||||
Financial liabilities |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
September 30, 2024 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
Borrowings (excluding lease liabilities) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
Lease liabilities |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
Trade payables, accrued expenses and other liabilities |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
Total financial liabilities |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
“Borrowings (excluding lease liabilities)” comprise convertible notes and royalty funding liabilities. Further details regarding classification of convertible notes as current liabilities in the consolidated statement of financial position are provided in Note 2, “Summary of Material Accounting Policies,” section “New and Amended Standards and Interpretations.” Expected maturity for royalty funding liabilities is based on anticipated amount and timing of future commercial revenue. Further details regarding the payment structure of the royalty funding agreements are provided above.
Note 11—Subsequent Events
No events have occurred after the balance sheet date that would influence the evaluation of these unaudited condensed consolidated interim financial statements.
F-17
ASCENDIS PHARMA A/S
MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND
RESULTS OF OPERATIONS
You should read the following discussion and analysis of our financial condition and results of operations in conjunction with our unaudited condensed consolidated interim financial statements, including the notes thereto, included with this report and the section contained in our Annual Report on Form 20-F for the year ended December 31, 2023– “Item 5. Operating and Financial Review and Prospects.” The following discussion is based on our financial information prepared in accordance with International Accounting Standard 34, “Interim Financial Reporting.” Certain information and disclosures normally included in the consolidated financial statements prepared in accordance with IFRS Accounting Standards (“IFRS”) have been condensed or omitted. IFRS as issued by the International Accounting Standards Board, and as adopted by the European Union, might differ in material respects from generally accepted accounting principles in other jurisdictions.
Special Note Regarding Forward-Looking Statements
This report contains forward-looking statements concerning our business, operations and financial performance and condition, as well as our plans, objectives and expectations for our business operations and financial performance and condition. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “predict,” “potential,” “positioned,” “seek,” “should,” “target,” “will,” “would,” and other similar expressions that are predictions or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, statements about:
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These forward-looking statements are based on senior management’s current expectations, estimates, forecasts and projections about our business and the industry in which we operate and involve known and unknown risks, uncertainties and other factors that are in some cases beyond our control. As a result, any or all of our forward-looking statements in this report may turn out to be inaccurate. Factors that may cause actual results to differ materially from current expectations include, among other things, those listed under the section in our Annual Report on Form 20-F for the year ended December 31, 2023 — “Item 3.D. Risk Factors.” You are urged to consider these factors carefully in evaluating the forward-looking statements. These forward-looking statements speak only as of the date of this report. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future. Given these risks and uncertainties, you are cautioned not to rely on such forward-looking statements as predictions of future events.
You should read this report and the documents that we reference in this report and have filed as exhibits to this report completely and with the understanding that our actual future results may be materially different from what we expect. You should also review the factors and risks we describe in the reports we will file or submit from time to time with the Securities and Exchange Commission after the date of this report. We qualify all of our forward-looking statements by these cautionary statements.
Overview
We are applying our innovative TransCon technology platform to build a leading, fully integrated, global biopharma company focused on making a meaningful difference in patients’ lives. Guided by our core values of Patients, Science, and Passion, we use our TransCon technologies to create new and potentially best-in-class therapies.
Our Vision
As announced in January 2024, Vision 2030 is our vision to achieve blockbuster status for multiple products and expand our engine for future innovation. This includes:
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Our products and product candidates combine our TransCon technologies with clinically validated parent drugs or pathways, with the goal of optimizing safety, efficacy, tolerability, and convenience.
We apply these technologies using our algorithm with the goal of creating product candidates with the potential to be best-in-class. Using this approach, we plan to expand our pipeline with Endocrinology Rare Disease product opportunities in large addressable markets. In addition, our vision is to pursue TransCon product opportunities in >$5B indications in other therapeutic areas and maximize value creation of these product opportunities through collaboration with therapeutic area market leaders. We believe our approach to product innovation may reduce the risks associated with traditional drug development.
Ascendis Algorithm for Product Innovation
When we apply our TransCon technologies to clinically validated parent drugs or pathways, we may benefit from established clinical safety and efficacy data, which we believe increases the probability of success compared to traditional drug development. As illustrated above, our algorithm for product innovation focuses on identifying indications that have an unmet medical need, have a clinically validated parent drug or pathway, are suitable to our TransCon technologies, have potential for creating a clearly differentiated product, have a potential established development pathway, and have the potential to address a large market.
Program Summaries
We currently have two marketed products and a diversified portfolio of four product candidates in clinical development in the areas of Endocrinology Rare Disease and Oncology, and we are working to apply our TransCon technology platform in additional therapeutic areas such as the glucagon-like peptide 1 (“GLP-1”) class, where we believe we have designed a potentially best-in-class, once-monthly program.
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TransCon Products and Product Candidates Pipeline
Other than the rights we have granted to Eyconis, Novo Nordisk, Teijin Limited, and VISEN as noted in this report, we hold worldwide rights to our TransCon technologies and, other than our royalty financing arrangements with Royalty Pharma as noted in this report, we owe no third-party royalty or milestone payment obligations with respect to our TransCon technologies, TransCon hGH, TransCon PTH or any of our other product candidates. The following chart lists our approved products and product candidates.
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We maintain an intellectual property portfolio comprising over 350 issued patents and over 550 patent applications as of June 30, 2024, which includes patents and patent applications applicable to our products and product candidates with claims directed to composition of matter, process, formulation and/or methods-of-use for our products and product candidates, including a product-specific device and core TransCon technologies. While our TransCon prodrugs may incorporate already approved parent drugs, TransCon hGH, TransCon PTH, and each of our other product candidates are new molecular entities and therefore eligible to be granted new intellectual property rights, including new composition of matter patents.
Global Commercialization Strategy
We are establishing a global presence to commercialize TransCon products and product candidates, if approved, to address patients’ unmet medical needs.
In the U.S., we have established a multi-faceted organization to support the ongoing commercialization of SKYTROFA, which will also serve as the foundation for future Endocrinology Rare Disease product launches in the U.S., including YORVIPATH.
In Europe, we are expanding our presence by building integrated organizations in select countries, which we call Europe Direct, beginning with Germany, where we have launched SKYTROFA and YORVIPATH. We are establishing commercial infrastructure in other Europe Direct country clusters, including DACH (Germany, Austria, Switzerland), France & BeNeLux (Belgium, the Netherlands, and Luxembourg), Iberia (Portugal and Spain), Italy, Nordics (Denmark, Norway, Sweden, Iceland, Finland), and the United Kingdom & Ireland.
Beyond the U.S. and Europe Direct, we are expanding global reach for our Endocrinology Rare Disease programs through exclusive distribution agreements with geographic market leaders, which we call International Markets. As of September 30, 2024, we have established seven such regional agreements:
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Finally, we are making our products commercially available in select markets through exclusive license agreements with partners with local development and commercialization expertise and infrastructure. In China, VISEN has exclusive license rights to develop and commercialize TransCon hGH, TransCon PTH, and TransCon CNP. In Japan, Teijin Limited has exclusive license rights to develop and commercialize TransCon hGH, TransCon PTH, and TransCon CNP.
TransCon Technologies
Overview
Our TransCon technologies are designed to combine the benefits of conventional prodrug and sustained release technologies to solve the fundamental limitations seen in other approaches to extending duration of a drug’s action in the body, with the goal of developing highly differentiated product candidates based on efficacy, safety, tolerability, and convenience. In addition to retaining the original mode of action of the parent drug and potentially supporting dosing frequency from daily up to six months or more, we believe that predictable release over time can improve treatment safety and efficacy, increase the likelihood of clinical development success, and provide intellectual property benefits.
TransCon molecules can have up to three components: a parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic pH and temperature conditions initiate the release of the active, unmodified parent drug in a predictable release manner.
Depending upon the type of TransCon carrier we employ, we can design our TransCon prodrugs for sustained localized or systemic delivery.
TransCon Technology Components
TransCon Carriers
Our TransCon technologies incorporate two carrier platforms that can be used to provide sustained localized or systemic drug exposure. These biocompatible carrier platforms include our TransCon systemic carriers and TransCon localized carriers (self-eliminating hydrogels). Our carriers inactivate and protect the drug through a shielding effect, which may prevent rapid excretion and degradation of the parent drug and enable benefits that include improved injection site tolerability, reduced systemic adverse effects, and low immunogenicity.
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TransCon Linkers
Our reversible TransCon linkers are designed to enable the transient conjugation of a broad range of therapeutics, including proteins, peptides, and small molecules, to our TransCon carriers. We have a large library of TransCon linkers that may be applicable to various types of parent drugs, and that can be tailored to potentially achieve half-life extension enabling daily, weekly, monthly, and half-yearly dosing and to customize the potential pharmacokinetic profile for each individual product candidate with the goal of optimizing the potential therapeutic effect. TransCon linkers are self-cleaving through a process called intra-molecular assisted cleavage, which causes the linker to release the unmodified parent drug. We can tailor the release properties of the linker to a given therapeutic indication and parent drug by modifying the linker structures. We believe the self-cleaving process of our linker avoids many of the shortcomings of conventional prodrug technologies, which often depend on metabolic processes, such as enzymatic degradation, to convert the prodrug into the active drug. The rate of metabolic conversion of prodrugs in these types of processes may differ between patients, and even within different tissues in the same patient. As a result, conventional prodrugs do not always offer predictable release of the parent drug. Our TransCon linkers are designed to predictably release an unmodified active parent drug at predetermined rates governed by physiological pH and temperature conditions, which are tightly regulated in the body. Consequently, we believe we can design our prodrugs to release the unmodified parent drug at predictable rates.
Parent Drugs
Our TransCon technologies are applicable across a broad range of therapeutic classes and are currently used to create potentially best-in-class long-acting product candidates based on proteins, peptides, and small molecules. By primarily focusing on biological targets that have been clinically validated, we can leverage available knowledge regarding a target’s activity. Based on this selective approach, we know what drug levels must be maintained in the body for optimal efficacy and safety, and we can design the release half-life and dosing frequency of our TransCon prodrugs to maintain these levels to achieve the desired pharmacological effect. We move a product candidate into development after it demonstrates the desired profile in non-clinical models. Furthermore, based on the established translational relationships between preclinical animal models and clinical efficacy, we believe experimental results generated in animal models are highly predictive of clinical results and reduce the development risk for our TransCon prodrugs. This strategy is designed to reduce risk and increase productivity.
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This approach has enabled us to develop two approved products and generate a pipeline of product candidates designed to address significant unmet medical needs and to become potential sources of significant revenue for our company. Because our TransCon technologies leverage clinically validated parent drugs or pathways, we believe we may benefit from a higher development and regulatory success rate compared to development of drug compounds without established biology.
TransCon Products – Endocrinology Rare Disease
TransCon Growth Hormone (hGH)
Market Opportunity for Recombinant Human Growth Hormone
Growth hormone deficiency is a serious orphan disease that affects both children and adults. Children with GHD are characterized by short stature, metabolic, and cardiovascular abnormalities, cognitive deficiencies, and poor quality of life. GHD in adults is associated with increased adiposity, or fat mass, as well as psychiatric-cognitive, cardiovascular, muscular, metabolic and skeletal abnormalities. In childhood and adolescence, growth hormone plays an essential role in normal longitudinal growth, muscle and bone strength, and distribution of body fat. In adults, growth hormone contributes to body composition, cardiovascular function, and bone health. The current standard of care for GHD has been daily subcutaneous injections of somatropin, a recombinant human growth hormone (“hGH”). These daily hGH therapies have been shown to be safe and well-tolerated.
In both therapy-compliant children and adults with GHD, daily subcutaneous injections of hGH result in improved body composition parameters, bone density, cardiovascular outcomes and quality of life. Growth hormone-deficient children who are fully adherent to their daily hGH treatment regimen may achieve a height in adulthood that is comparable to that of their family members and national norms.
Despite the demonstrated benefits of daily hGH therapy, many GHD patients are not adequately treated, and adherence continues to be a challenge, as reported in a 2021 paper published by Kaplowitz et al. (Kaplowitz P, Manjelievskaia J, Lopez-Gonzalez L, et al. Economic burden of growth hormone deficiency in a US pediatric population. J Manag Care Spec Pharm. 2021; 27(8):1118-1128). The observational retrospective cohort analysis utilized administrative claims data from two databases on over 20,000 pediatric patients diagnosed with GHD. Approximately 68% of commercial patients and approximately 63% of Medicaid patients received daily growth hormone treatment, whereas approximately 32% of commercial patients and approximately 37% of Medicaid patients were untreated. In addition, mean adherence as measured by proportions of days covered, which is defined as the number of days covered by any daily growth hormone prescription during the follow-up period, was approximately 60% in the commercial cohort and approximately 50% in the Medicaid cohort. Only 32% of commercial and 18% of Medicaid patients reported adherence rates greater than 80%.
For adult patients with GHD, underdiagnosis and undertreatment are also a concern. Untreated adult GHD (“AGHD”) patients can experience reduced quality of life and increased risk of morbidity and mortality. A retrospective cohort study presented at ENDO 2023 analyzed an electronic health records database and selected adult patients with suspected AGHD. Of the 51,588 patients with suspected AGHD, fewer than 4% were treated with growth hormone.
Since the introduction of hGH in 1981, a number of the world’s largest pharmaceutical companies have developed and marketed daily-administered hGH products. All currently marketed daily hGH products in the United States – Norditropin® (Novo Nordisk A/S), Humatrope® (Eli Lilly and Company), Genotropin® (Pfizer Inc.), Zomacton® (Ferring Pharmaceuticals, Inc.) and Omnitrope® (Sandoz GmbH) – contain unmodified somatropin (“hGH”) and are administered by subcutaneous injections. The global market for daily hGH products is largely composed of products from Novo Nordisk, Pfizer, Eli Lilly, Sandoz, and Merck KGaA, which together account for most of the global market share.
Primary indications for hGH in children are GHD, idiopathic short stature, chronic kidney disease, Prader-Willi syndrome, small for gestational age, and Turner syndrome. In adults, primary indications for hGH include GHD and AIDS-induced weight loss. We estimate pediatric indications comprise up to 90% of the current total hGH market, of which approximately half is for pediatric GHD.
Competitive Landscape for Long-Acting Growth Hormone Therapies
Since the 1990s, the pharmaceutical industry has employed various approaches to develop long-acting growth hormone products to reduce the burden of daily injections on patients and increase patient compliance with the dosing regimen. These approaches generally fall into two categories: unmodified somatropin (“hGH”) and permanent modification of growth hormone:
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Novo Nordisk received regulatory approval in various countries and regions including the U.S., Japan, and EU for once-weekly somapacitan (SOGROYA®) in adult and pediatric patients with GHD.
Pfizer (in collaboration with OPKO Health Inc.) received regulatory approval of once-weekly somatrogon (NGENLA) in various countries and regions including the U.S., Japan, and EU for pediatric GHD.
A permanently PEGylated long-acting growth hormone developed by GeneScience Pharmaceuticals Co., Ltd. (Jintrolong®) is available in China and the Somatropin Biopartners product (LB03002) is available in Korea. Other experimental growth hormone therapies based on permanent modification are in different stages of clinical development by various companies, including Genexine Inc., I-MAB, Amoytop, UnionGene, Anhui Anke Biotechnology, Alteogen, and JCR Pharmaceuticals Co., Ltd.
Our Solution: TransCon hGH
TransCon hGH is a prodrug composed of somatropin that is transiently bound to a carrier by a proprietary linker. TransCon hGH is administered once weekly and is designed to maintain the same mode of action as daily therapies by providing sustained release of active, unmodified somatropin, the same recombinant growth hormone molecule used in the daily hGH therapies that are the current standard of care.
TransCon Growth Hormone (hGH) for Pediatric GHD
TransCon hGH, marketed under the brand name SKYTROFA® (lonapegsomatropin-tcgd), received regulatory approval in the U.S. for the treatment of pediatric patients one year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone, also known as GHD. SKYTROFA has been commercially available for prescription in the United States since October 2021. In the EU, Norway, Iceland, Lichtenstein, and Great Britain (covering England, Wales, Scotland), we received marketing authorization for TransCon hGH – known by its brand name SKYTROFA (lonapegsomatropin) – as a once-weekly subcutaneous injection for the treatment of children and adolescents aged 3 to 18 years with growth failure due to insufficient secretion of endogenous growth hormone. SKYTROFA has been commercially available for prescription in Germany since September 2023.
In September 2023, we announced topline results from the completed enliGHten Trial, an open-label extension trial evaluating the long-term safety and efficacy of TransCon hGH as a once-weekly treatment for children and adolescents with GHD. The enliGHten Trial enrolled 298 participants (mean age 10.3 years) from the Phase 3 heiGHt Trial of treatment-naïve pediatric GHD patients and the Phase 3 fliGHt Trial of pediatric GHD patients switching from daily somatropin treatment. Patients in these trials received a total of up to 6 years of treatment with TransCon hGH. At the time of the enliGHten Trial closure, 81 participants were designated as treatment completers, based on their physician’s determination that treatment for pediatric GHD was no longer required. Of these treatment completers, 59% met or exceeded their average parental height standard deviation score (“SDS”), with mean TransCon hGH treatment duration of 3.2 years.
Clinical Trial of TransCon hGH in Japanese Pediatric GHD
In our ongoing Phase 3 riGHt Trial, we are evaluating TransCon hGH as a treatment in Japanese children with GHD. The primary objective of the riGHt Trial is to evaluate and compare the annualized height velocity of approximately 40 Japanese prepubertal children with GHD treated with once-weekly TransCon hGH to that of children treated with a commercially available daily hGH formulation at 52 weeks. Enrollment in the riGHt trial was completed during the fourth quarter of 2023.
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Proprietary Auto-Injector
SKYTROFA includes the SKYTROFA®Auto-Injector and cartridges. The auto-injector provides for room temperature storage, includes an empty-all design, and is expected to last for at least four years. The device enables a single, low-volume injection of less than 0.6 mL for the majority of patients with a thin, 31-gauge needle that is only 4 millimeters in length, which is comparable to needles used to administer daily hGH. We are also working on strategies that will enable the auto-injector to integrate with the digital healthcare system, including Bluetooth connectivity features to allow for easy tracking of dosing adherence over time.
Figure: Our state-of-the-art auto-injector is designed to improve treatment compliance for children with GHD.
TransCon Product Candidates – Endocrinology Rare Diseases
TransCon Growth Hormone (hGH) for Other Indications
Clinical Development in Adults
In September 2024, we announced the submission of a supplemental Biologics License Application to the FDA for TransCon hGH for the treatment of adults with GHD. The submission is based on results from foresiGHt, a Phase 3 randomized, parallel-arm, placebo-controlled (double-blind), and active-controlled (open-label) trial that compared the efficacy and safety of weekly TransCon hGH with weekly placebo and daily hGH in adults with GHD.
In December 2023, we announced positive topline results from foresiGHt. The trial aims to evaluate the metabolic benefits of TransCon hGH in adults, with the primary objective to evaluate change in trunk fat percentage.
The foresiGHt Trial evaluated 259 adults with GHD aged 23 to 80 years old, randomized 1:1:1, titrated to receive a target fixed dose of TransCon hGH, placebo, or daily hGH based on age and oral estrogen intake, with approximately equivalent hGH mg/week for TransCon hGH and daily hGH.
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Other Development Plans
In June 2022, we initiated the Phase 2 New InsiGHTS Trial in the U.S. to evaluate TransCon hGH in Turner syndrome. In this trial, we are evaluating higher doses of TransCon hGH and daily hGH for Turner syndrome compared to doses for pediatric or adult GHD. Topline results from New InsiGHTS are expected in the fourth quarter of 2024. In addition, we are investigating other potential indications for TransCon hGH where we believe a long-acting hGH therapy may offer benefits to patients with rare growth disorders, including in combination with our TransCon CNP product candidate.
TransCon PTH
Market Opportunity in Hypoparathyroidism
Hypoparathyroidism is a rare endocrine disease characterized by insufficient levels of parathyroid hormone (“PTH”). Most patients with hypoparathyroidism develop the condition following damage to or accidental removal of the parathyroid glands during thyroid surgery. Post-surgical hypoparathyroidism accounts for the majority of cases (70-80%); other etiologies include autoimmune disorders, genetic disorders such as autosomal dominant hypocalcemia type 1, and idiopathic causes. Conventional therapy with oral calcium and active vitamin D (also called calcitriol) does not effectively address the short-term symptoms, long-term complications, or quality-of-life impacts of hypoparathyroidism.
Short-term symptoms include weakness, severe muscle cramps (tetany), abnormal sensations such as tingling, burning, and numbness (paresthesia), memory loss, impaired judgment, and headache. Patients often experience decreased quality of life, and prolonged use of conventional therapy may increase risk of major complications, such as calcium deposits in the brain, blood vessels, eyes, and other soft tissues. According to a recent systematic literature review, chronic hypoparathyroidism treated with conventional therapy is associated with higher rates of renal complications compared to the general population, such as nephrolithiasis (up to 36%), nephrocalcinosis (up to 38%), and chronic kidney disease (up to 41%).
Hypoparathyroidism also poses a high burden on the healthcare system despite current conventional therapy. For example, one survey of 374 patients showed that 72% experienced more than ten symptoms in the preceding twelve months, with symptoms experienced for a mean of 13 ± 9 hours a day. Other studies showed that 79% of hypoparathyroidism cases require hospitalizations and that patients with the disease have a four-fold increase in the risk of renal disease compared to healthy controls. Patients often experience decreased quality of life. We conducted a survey of 42 patients, which found that 100% of patients reported negative psychological impacts, interference with daily life, and impact on physical functioning from hypoparathyroidism, and that 76% were either no longer able to work or experienced interference with work productivity.
The 2022 Guidelines from the Second International Workshop addressing the prevention, diagnosis, and management of hypoparathyroidism was published in September 2022 in the Journal of Bone and Mineral Research and authored by leading clinicians from North America, Europe, and Asia. The authors suggest consideration of PTH replacement therapy in patients whose hypoparathyroidism is inadequately controlled with conventional therapy. Inadequate control is considered to be any one of the following: symptomatic hypocalcemia, hyperphosphatemia, renal insufficiency, hypercalciuria, or poor quality of life. In addition, the guideline indicates that individuals with poor compliance, malabsorption, or intolerant of large doses of calcium and active vitamin D may also benefit from PTH replacement therapy. Based on this current guideline, we believe PTH replacement therapy could be applicable to most patients with hypoparathyroidism.
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In 2015, NATPARA® (parathyroid hormone) for injection was approved in the U.S. for once-daily subcutaneous injection as an adjunct to vitamin D and calcium in patients with hypoparathyroidism. NATPARA was voluntarily recalled in September 2019 in the U.S. and is now only available to a limited number of patients through a Special Use Program offered by its manufacturer, Takeda. In October 2022, Takeda announced that it will discontinue manufacturing NATPARA/NATPAR globally by the end of 2024.
We are also aware of several academic groups and companies working on making longer-acting agonists of the PTH receptor. In addition, other companies and groups are developing or commercializing therapies for hypoparathyroidism, including Calcilytix (a BridgeBio company), Entera Bio, Extend Biosciences, Massachusetts General Hospital, Amolyt Pharma (acquired by AstraZeneca), and MBX Biosciences.
Teriparatide, PTH (1-34), approved since 2002 for the treatment of osteoporosis, has sometimes been used for treatment of hypoparathyroidism using multiple daily injections, despite not being approved for this indication. Clinical research conducted by the U.S. National Institutes of Health in subjects receiving continuous exposure to PTH (1-34), administered by an infusion pump, demonstrated simultaneous normalization of serum calcium and urinary calcium, as well as normalization of bone turnover.
We estimate hypoparathyroidism affects over 250,000 patients in the U.S. and Europe. In the U.S., we estimate hypoparathyroidism affects approximately 70,000 to 90,000 patients, including 4,000 to 5,000 patients who we estimate have previously been treated with PTH therapy. In Germany, we estimate hypoparathyroidism affects approximately 70,000 patients. Outside of Germany, we estimate hypoparathyroidism affects over 100,000 patients in the rest of Europe.
Our Solution: TransCon PTH
TransCon PTH (palopegteriparatide) is a prodrug of PTH (1-34) that is designed to be dosed once-daily to achieve and maintain a steady concentration of PTH in the bloodstream within the normal range. TransCon PTH is designed to provide PTH in the physiological range for 24 hours per day, thereby more fully addressing aspects of the disease, including normalizing serum and urinary calcium and serum phosphate levels.
By providing steady levels of PTH in the physiological range, we believe TransCon PTH can address the fundamental limitations of PTH therapies with short half-life molecules and become a highly differentiated therapy for hypoparathyroidism.
TransCon PTH for adults with hypoparathyroidism
In November 2023, TransCon PTH received regulatory approval in the EU and European Economic Area and is marketed as YORVIPATH® (palopegteriparatide), a parathyroid hormone replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. In April 2024, TransCon PTH received regulatory approval in Great Britain as a PTH replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. In August 2024, the U.S. FDA approved TransCon PTH for the treatment of hypoparathyroidism in adults. We anticipate initial supply for the U.S. market will be available in mid-January 2025.
In January 2024, we announced that YORVIPATH is commercially available in Germany and Austria, and we began shipping to customers in February 2024. In April 2024, we announced that the United Kingdom’s Medicines & Healthcare products Regulatory Agency granted YORVIPATH Orphan Drug status.
Clinical Development of TransCon PTH for Adult Hypoparathyroidism
Our ongoing Phase 3 PaTHway Trial, Phase 3 PaTHway Japan Trial, and Phase 2 PaTH Forward Trial continue in the open-label extension portion to collect long-term data.
In September 2024, the FDA granted Orphan Drug exclusivity to YORVIPATH, providing seven years of market exclusivity for YORVIPATH in the United States for the treatment of hypoparathyroidism in adults.
In May 2024, we announced two-year results from a post-hoc analysis of the Phase 3 PaTHway Trial demonstrating significant and sustained improvements in renal function in adults with chronic hypoparathyroidism treated with TransCon PTH. The post-hoc analysis examined the impact of treatment with TransCon PTH on renal function using estimated glomerular filtration rate (“eGFR”) through Week 104 (n=76) of PaTHway, a Phase 3 double-blind, placebo-controlled trial of 82 dosed adults with chronic hypoparathyroidism randomized 3:1 (TransCon PTH:placebo; both arms initially co-administered with conventional therapy of active vitamin D and oral calcium), with a 26-week blinded period followed by an ongoing 156-week open-label extension period. Across both treatment arms, TransCon PTH treatment resulted in a mean eGFR increase of 8.9 mL/min/1.73m2 (p<0.0001) from baseline at Week 52, sustained at Week 104 with a mean change from baseline of 9.0 mL/min/1.73m2 (p<0.0001). Treatment was generally well-tolerated, with no new safety signals.
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eGFR* Change from Baseline by Study Arm |
|||||||
|
Baseline |
Week 26 |
Week 52 |
Week 104 |
|||
Study Arm |
eGFR |
|
Mean (p value) |
|
Mean |
|
Mean |
TransCon PTH / TransCon PTH |
eGFR < 60 |
19 |
+11.4 |
19 |
+11.5 |
18 |
+13.4 |
eGFR ≥ 60 |
41 |
+6.3 |
40 |
+8.6 |
40 |
+6.9 |
|
All |
60 |
+7.9 (p<0.0001) |
59 |
+9.3 |
58 |
+8.9 |
|
Placebo |
eGFR < 60 |
4 |
+0.1 |
4 |
+11.7 |
4 |
+15.6 |
eGFR ≥ 60 |
15 |
-2.4 |
15 |
+6.5 |
14 |
+7.6 |
|
All |
19 |
-1.9 (p=0.3468) |
19 |
+7.6 (p=0.0014) |
18 |
+9.4 |
|
*eGFR (an assessment of kidney filtering capacity) was calculated by the trial’s central lab using the Modification of Diet in Renal Disease Study Group (MDRD) equation (Levey, Ann Intern Med 2006). An eGFR level <60 mL/min/1.73m2 is considered the threshold for impaired kidney function.
**Patients in the placebo arm switched to TransCon PTH following the Week 26 visit.
TransCon PTH treatment was associated with clinically meaningful increases (≥ 5 mL/min/1.73 m2) in eGFR within 26 weeks that were sustained through Week 104 of PaTHway:
Proportion of Participants (%) with ≥ 5 and ≥ 10 mL/min/1.73 m2 Increases in eGFR |
||||||
eGFR Change from Baseline |
All Participants |
|||||
TransCon PTH / TransCon PTH |
Placebo (first 26 weeks) / TransCon PTH** |
|||||
Week 26 |
Week 52 |
Week 104 |
Week 26 |
Week 52 |
Week 104 |
|
PTH |
PTH |
PTH |
Placebo |
Switch to PTH |
Switch to PTH |
|
≥ 5 mL/min/1.73 m2 |
57% |
64% |
61% |
24% |
52% |
62% |
≥ 10 mL/min/1.73 m2 |
43% |
43% |
46% |
10% |
29% |
38% |
|
||||||
eGFR Change from Baseline |
Participants with Baseline eGFR < 60 mL/min/1.73 m2 |
|||||
TransCon PTH / TransCon PTH |
Placebo (first 26 weeks) / TransCon PTH** |
|||||
Week 26 |
Week 52 |
Week 104 |
Week 26 |
Week 52 |
Week 104 |
|
PTH |
PTH |
PTH |
Placebo |
Switch to PTH |
Switch to PTH |
|
≥ 5 mL/min/1.73 m2 |
74% |
68% |
74% |
25% |
100% |
100% |
≥ 10 mL/min/1.73 m2 |
47% |
42% |
53% |
0% |
75% |
75% |
*Percentages were calculated based on all participants. Patients who did not have an eGFR assessment at the visit were still included in the denominator.
**Patients in the placebo arm switched to TransCon PTH following the Week 26 visit.
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In June 2023, we announced one-year (Week 52) data from the open-label extension (“OLE”) portion of the Phase 3 PaTHway Trial of TransCon PTH in adults with hypoparathyroidism. PaTHway is a Phase 3 trial of TransCon PTH with a placebo-controlled 26-week blinded portion and a 156-week OLE portion, designed to evaluate the long-term efficacy and safety of TransCon PTH as a potential hormone therapy for adult patients diagnosed with hypoparathyroidism. Of the 82 study participants dosed, 79 completed blinded treatment and entered the OLE, and 78 (59 TransCon PTH/TransCon PTH, 19 placebo/TransCon PTH) completed Week 52. The data showed that treatment with TransCon PTH resulted in sustained improvements through Week 52, as well as safety and tolerability similar to that reported for the initial 26-week blinded portion of the trial. As of September 30, 2024, 74 out of 79 patients continue in the OLE and have exceeded three years of follow-up in the PaTHway Trial.
On January 8, 2023, we announced topline data from PaTHway Japan, a single-arm Phase 3 trial to evaluate the safety, tolerability, and efficacy of TransCon PTH in adults with hypoparathyroidism. The study achieved its primary objective, with topline results consistent with our trials in North America and the EU. Twelve out of thirteen patients met the primary multi-component endpoint, which was defined as serum calcium levels in the normal range (8.3–10.6 mg/dL) and independence from conventional therapy (no active vitamin D and ≤600 mg/day of calcium). In this trial, TransCon PTH was generally well-tolerated, with no discontinuations related to study drug. As of September 30, 2024, 12 patients continue in the ongoing 3-year extension portion of the PaTHway Japan Trial.
In December 2022, the FDA allowed us to initiate a U.S. expanded access program (“EAP”) for TransCon PTH for eligible adult patients with hypoparathyroidism with prior PTH treatment experience. This EAP program is ongoing.
In September 2022, we announced new Week 110 data from the Phase 2 PaTH Forward Trial showing that long-term therapy with TransCon PTH provided a durable response in adult patients with hypoparathyroidism, as evidenced by maintenance of normal mean serum calcium levels and 93% of patients achieving independence from conventional therapy (no active vitamin D and ≤600 mg/day of calcium). Fifty-seven subjects exceeded three years of follow-up in the PaTH Forward Trial. As of September 30, 2024, 56 out of the 59 patients originally enrolled in the trial continued in the OLE portion and have exceeded four and a half years of follow-up. Three patients withdrew from the trial for reasons unrelated to safety or efficacy of the study drug.
In March 2022, we announced that top-line data from the randomized, double-blind, placebo-controlled portion of the Phase 3 PaTHway Trial of TransCon PTH in adults with hypoparathyroidism demonstrated statistically significant higher proportion of participants treated with TransCon PTH achieved the primary multi-component endpoint compared to placebo. The primary endpoint, defined as serum calcium levels in the normal range (8.3–10.6 mg/dL) and independence from conventional therapy (no active vitamin D and ≤600 mg/day of calcium) with no increase in prescribed study drug within the 4 weeks prior to the Week 26 visit, was achieved by 78.7% of TransCon PTH-treated patients (48 of 61), compared to 4.8% for patients (1 of 21) in control group (p-value <0.0001). In addition, all key pre-specified secondary endpoints were met with statistical significance. TransCon PTH was generally well tolerated, with no discontinuations related to study drug. Three patients discontinued during the treatment period, two from the placebo arm and one from the TransCon PTH arm. TransCon PTH-treated patients showed a mean decrease in 24-hour urine calcium excretion into the normal range.
In April 2020, we announced top-line data from the four-week fixed dose, double-blinded portion of PaTH Forward, a global Phase 2 trial evaluating the safety, tolerability and efficacy of TransCon PTH in adult subjects with hypoparathyroidism. A total of 59 subjects were randomized in a blinded manner to receive fixed doses of TransCon PTH at 15, 18 or 21 µg/day or placebo for four weeks using a ready-to-use prefilled pen injector planned for commercial presentation. All doses of TransCon PTH were well-tolerated, and no serious or severe treatment-related adverse events (“TEAEs”) were observed at any point. No treatment-emergent adverse events led to discontinuation of study drug, and the overall incidence of TEAEs was comparable between TransCon PTH and placebo. Additionally, there were no drop-outs during the four-week fixed dose period.
In October 2020, we were granted Orphan Designation (“OD”) by the European Commission (“EC”) for TransCon PTH for the treatment of hypoparathyroidism. In July 2021, the Ministry of Health, Labour and Welfare in Japan granted ODD to TransCon PTH for the treatment of hypoparathyroidism.
TransCon CNP
Market Opportunity in Achondroplasia
Achondroplasia is the most common genetic form of skeletal dysplasia leading to disproportionate short stature and is associated with a well-delineated range of clinical complications and manifestations, occurring in about one in 10,000 to 30,000 newborns or approximately 250,000 worldwide. Achondroplasia results in severe skeletal complications and comorbidities including spinal stenosis due to premature fusion of the foramen magnum, sleep apnea, chronic ear infections, and muscular complications. Patients often face multiple surgeries to alleviate its many complications. There is significant unmet need for treatments that ameliorate complications and improve quality of life in achondroplasia.
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Achondroplasia is primarily caused by gain-of-function variants of the FGFR3 gene resulting in constitutive activation of FGFR3 that leads to an imbalance in the effects of the FGFR3 and C-type natriuretic peptide (“CNP”) signaling pathways. In achondroplasia, mutations in FGFR3 result in constitutive activation, suppressing the proliferation and differentiation of chondrocytes resulting in improper cartilage to bone conversion in the growth plate, and dysfunction in the skeletal muscle. Preclinical and clinical data show that the CNP pathway helps to counteract the effects of the FGFR3 mutation downstream.
In November 2021, BioMarin Pharmaceutical Inc.’s VOXZOGO® (vosoritide) was approved by the FDA and is indicated to increase linear growth in pediatric patients with achondroplasia with open epiphyses. Other companies that are developing therapies for achondroplasia include QED Therapeutics (a BridgeBio company), Sanofi, Ribomic, Tyra Biosciences, and ProLynx.
Changing the Treatment Paradigm of Achondroplasia
Clinical manifestations of achondroplasia are associated with significant, potentially life-threatening complications, and reduced quality of life. While achondroplasia has historically been considered a growth disorder, secondary manifestations beyond linear growth, including reduced muscle strength and stamina, suggest that achondroplasia is also a muscle disorder.
ACH-AE: Increased incidence of Achondroplasia-related Adverse Events.
HRQoL: Reduced Health-Related Quality of Life; Height; Reduced height. Muscle Strength/Stamina; Reduced muscular functionality, including reduced strength and stamina.
Our Solution: TransCon CNP
TransCon CNP (navepegritide) is an investigational prodrug of CNP administered once weekly and designed to provide sustained release of active CNP supporting continuous exposure for the treatment of achondroplasia. TransCon CNP is designed to provide effective shielding of CNP from neutral endopeptidase degradation in subcutaneous tissue and the blood compartment, minimize binding of CNP to the NPR-C receptor to decrease clearance, reduce binding of CNP to the NPR-B receptor in the cardiovascular system to avoid hypotension, and release unmodified CNP, which is small enough in size to allow effective penetration into growth plates. Shorter-acting CNP and CNP analogs in development have resulted in high Cmax levels that may cause adverse cardiovascular events. We believe the therapeutically sustained release of TransCon CNP offers advantages that may mitigate this issue, leading to more constant CNP exposure at lower Cmax to correlate with better therapeutic outcomes.
Clinical Development of TransCon CNP for Achondroplasia
Our ongoing pivotal ApproaCH Trial, ACcomplisH Trial, our long-term extension trial AttaCH, and COACH, are evaluating the safety and efficacy of TransCon CNP in children with achondroplasia. The ongoing reACHin Trial is evaluating the safety, tolerability, and efficacy of TransCon CNP in infants with achondroplasia (aged 0 to < 2 years at the time of randomization).
In September 2024, we announced topline data from ApproaCH, a pivotal, multicenter, randomized, double-blind, placebo-controlled trial of once-weekly TransCon CNP versus placebo in 84 children (aged 2 to 11 years) with achondroplasia. Participants were randomized 2:1 to receive TransCon CNP 100µg/kg/week or placebo for 52 weeks in the double-blind period, after which all participants could choose to receive TransCon CNP at the 100µg/kg/week dose in an ongoing open-label extension. In the trial, children treated with once-weekly TransCon CNP demonstrated annualized growth velocity (“AGV”) superior to those treated with placebo. TransCon CNP also demonstrated statistically significant improvements in other growth parameters, including height Z-score and change from baseline AGV.
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Highlights of the ApproaCH Trial Topline Data
Primary Endpoint
AGV Change from Baseline
Secondary Endpoints
Safety Summary
We plan to submit a New Drug Application (“NDA”) to the FDA for TransCon CNP for the treatment of children with achondroplasia during the first quarter of 2025 and a Marketing Authorisation Application (“MAA”) for the treatment of children with achondroplasia to the European Medicines Agency during the third quarter of 2025.
In December 2023, we announced new analyses demonstrating benefits beyond linear growth from the blinded and ongoing OLE portions of ACcomplisH, a Phase 2 randomized, double-blind, placebo-controlled, dose-escalation trial of TransCon CNP in children aged 2 to 10 years with achondroplasia. In the trial, all 57 patients have now completed one year of treatment with TransCon CNP at 100 µg/kg/week, the dose agreed with regulatory agencies for the active arm in our pivotal ApproaCH Trial.
We analyzed available data for patients who only received TransCon CNP at the 100 µg/kg/week dose in either blinded or OLE part and were treated for one year (n=19), compared to those administered placebo for one year (n=15). Results showed that these TransCon CNP-treated patients (data available for 9-16 patients) showed significant improvements in health-related quality of life and disease impacts compared to those receiving placebo (data available for 5-13 patients).
Assessments were performed with the SF-10 (a 10-item non-disease specific survey of a child’s functional health and well-being that is validated in children aged 5 years and older) and the Achondroplasia Child Experience Measure (“ACEM”) a condition-specific clinical outcome measure that assesses the impact of achondroplasia on a child’s health-related quality of life, with statistically significant improved outcome in TransCon CNP-treatment versus placebo for:
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The 46 children switching from placebo or a lower dose of TransCon CNP to the 100 µg/kg/week dose in the OLE demonstrated improved growth after one year of treatment, similar to the growth benefits seen in the 11 children treated with 100 µg/kg/week in the one-year randomized, double-blind period of ACcomplisH.
While the CNP pathway may restore normal growth and skeletal muscle function, delayed initiation of therapy could lead to a permanent height deficit. Clinical use of daily growth hormone injection has consistently demonstrated growth improvements in children with achondroplasia, including catch up growth; however, without reports of benefits beyond linear growth. We believe use of TransCon hGH and TransCon CNP together once per week could enable catch up growth beyond normal growth while maintaining benefits on skeletal muscle of continuous CNP exposure. During the fourth quarter of 2023, we filed a Clinical Trial Application for COACH, a Phase 2 open-label single-arm trial evaluating TransCon CNP and TransCon hGH in children with achondroplasia (age 2 to 11 years). The primary objective is to evaluate the treatment effect on linear growth and safety. Secondary objectives are to evaluate treatment effect on quality of life, radiological endpoints, physical functioning, and body composition. The trial plans to enroll approximately 18 patients (treatment naïve, n=12; prior treatment with TransCon CNP (100 µg/kg/week) for at least 1 year, n=6). Week 26 topline data from the COACH Trial are expected in the second quarter of 2025.
During the third quarter of 2023, we filed an IND amendment with the FDA to initiate reACHin, a Phase 2, multicenter, double-blind, randomized, placebo-controlled trial, designed to evaluate the safety, tolerability, and efficacy of 100 μg/kg of TransCon CNP once-weekly for 52 weeks in infants with achondroplasia, aged 0 to < 2 years at the time of randomization.
In September 2023, we announced completion of enrollment in ApproaCH with a total of 84 subjects randomized. U.S. and EU regulatory agencies have endorsed ApproaCH, a global randomized, double-blind, placebo-controlled trial in children aged 2 to 11 years with achondroplasia, as a pivotal Phase 3 trial. The primary endpoint of the trial is annualized growth velocity at 52 weeks with additional endpoints analyzing achondroplasia-related co-morbidities and quality of life. Topline results from the ApproaCH trial are expected in the third quarter of 2024. In addition, we intend to use the results from ApproaCH in connection with a planned NDA submission to the FDA for TransCon CNP for children with achondroplasia (age 2 to 11 years) in the first quarter of 2025.
In November 2022, we announced topline results from ACcomplisH, a Phase 2 randomized, double-blind, placebo-controlled, dose-escalation trial evaluating the safety and efficacy of once-weekly TransCon CNP compared to placebo in children with achondroplasia aged 2 to 10 years old.
The ACcomplisH Trial evaluated 57 children with achondroplasia aged 2 to 10 years old, randomized in a 3:1 ratio to receive either sequential ascending doses of once-weekly TransCon CNP (6 µg/kg/week, 20 µg/kg/week, 50 µg/kg/week, 100 µg/kg/week) or placebo for 52 weeks. The trial met its primary objectives, demonstrating that TransCon CNP at 100 µg/kg/week (n=11) was superior to placebo (n=15) on the primary efficacy endpoint of annualized growth velocity (“AGV”) at 52 weeks (p=0.0218). All 57 randomized children completed the blinded portion of ACcomplisH and continued in the OLE portion of ACcomplisH at the 100 µg/kg/week dose. As of September 30, 2024, 54 patients completed the OLE portion of the ACcomplisH Trial; 2 patients prematurely withdrew during the OLE. From ACcomplisH OLE, 52 patients transitioned into the Phase 2 AttaCH Trial, a multicenter, long-term, open-label extension trial to continue treatment with TransCon CNP 100 µg/kg/week and 2 patients transitioned into COACH, a TransCon CNP/TransCon hGH combination trial. In AttaCH, 42 patients are ongoing on long-term OLE treatment; 3 patients have prematurely withdrawn from treatment and 7 patients transitioned into COACH.
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In 2019, we initiated the ACHieve Study, a five-year, multi-center natural history study designed to gain insight into the experiences of pediatric patients with achondroplasia. ACHieve was designed to evaluate growth velocity, body proportionality, and comorbidities over time in children with achondroplasia up to eight years old. No study medication was administered in the ACHieve Study. The study ended in the first quarter of 2024. We plan to make the results available in 2025.
In February 2019, we were granted ODD by the FDA for TransCon CNP for the treatment of achondroplasia. In July 2020, we received OD from the EC for TransCon CNP for the treatment of achondroplasia.
TransCon Product Candidates—Oncology
Market Opportunity in Oncology
Cancer continues to be one of the leading causes of mortality. Improved understanding of the cellular and molecular mechanisms involved in anti-tumor immune responses has fueled the rapid growth of immuno-oncology therapeutics. Immune checkpoint inhibitors, such as anti-PD-(L)1 and anti-CTLA-4 antibodies, have provided new therapeutic options for patients.
Despite recent advances, a high need for new treatment options remains for patients who do not respond or respond inadequately to current therapies. In addition to insufficient efficacy, many current treatments are limited by toxicities that result in dose reductions, treatment discontinuations, or long-term health risks to patients.
We believe that one approach to improving efficacy while limiting adverse events is to create long-acting product candidates using our sustained systemic release TransCon technology, allowing for more consistent circulating drug levels and potentially avoiding high peak concentrations that are often associated with toxicity.
Another approach is to target the drug activity into tumors via intratumoral injection using our sustained localized release TransCon hydrogel technology, aiming for high activity in the tumor microenvironment while limiting systemic adverse events. While one intratumoral treatment has been approved for the local treatment of recurrent melanoma, the overall success of intratumoral treatments has been limited to date. This is likely partly due to lack of prolonged intratumoral exposure of active drug levels, resulting in the potential need for more frequent dosing.
Our Solution: TransCon Technologies for Oncology
We believe prolonging the therapeutic activity and targeting the drug activity to the relevant cell types and tissues have the potential to improve treatment outcomes. We believe TransCon is well-suited to improve cancer treatments given the large number of validated targets with known limitations. By applying our unique algorithm for product innovation to clinically validated targets and pathways, we believe TransCon has the potential to improve outcomes currently limited by suboptimal efficacy and systemic toxicity.
We believe TransCon technologies may have the potential to increase the efficacy of small molecules, peptides and proteins without increasing toxicity, which could offer the potential to treat more patients with new combination and multi-agent regimens that would not otherwise be feasible.
We are currently investigating two clinical-stage product candidates designed to activate the patient’s own immune system to eradicate malignant cells. We believe our approach, if successfully developed, has the potential to improve the efficacy of systemically administered, clinically validated therapies while limiting adverse effects.
Similarly, with the potential to achieve sustained local release at predictable levels, we believe TransCon hydrogel product candidates may allow for improved efficacy and reduced dosing frequency of intratumorally administered therapies, potentially enabling treatments of multiple tumor types, including those that cannot be easily accessed for frequent injection.
Development of TransCon Product Candidates in Oncology
Our TransCon product candidates in oncology are designed to provide sustained systemic or intratumoral administration, which we believe could provide potent and durable anti-tumor efficacy. Our nonclinical studies have shown sustained activation of cytotoxic immune cells that resulted in robust anti-tumor responses by TransCon product candidates using infrequent administration.
Two of our oncology product candidates, TransCon TLR7/8 Agonist and TransCon IL-2 b/g, are now in clinical development. In addition, we believe that a combination of TransCon TLR7/8 Agonist and TransCon IL-2 b/g may have the potential to produce greater anti-tumor activity than either candidate alone.
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TransCon TLR7/8 Agonist for sustained localized release
TransCon TLR7/8 Agonist is an investigational long-acting prodrug, designed for sustained intratumoral release of resiquimod, a small molecule agonist of TLR 7 and 8. It is designed to provide sustained and potent activation of the innate immune system in the tumor and tumor draining lymph node for weeks following a single intratumoral injection and to have a low risk of systemic toxicity. The transcendIT-101 Trial, a Phase 1/2 clinical trial to evaluate the safety and efficacy of TransCon TLR7/8 Agonist in locally advanced or metastatic solid tumors, alone or in combination with pembrolizumab, has completed dose escalation and has enrolled patients in four indication-specific cohorts where increased TLR7/8 activity has potential to improve innate and adaptive immune activation and host defense against cancers: head and neck squamous cell carcinoma (“HNSCC”), HPV-associated cancers, melanoma, and cutaneous squamous cell carcinoma (“cSCC”).
In May 2023, we announced additional follow-up from the transcendIT-101 Trial indicating further clinical activity in patients receiving TransCon TLR7/8 Agonist as monotherapy or in combination with pembrolizumab. Enrollment continues in the Phase 2 portion of transcendIT-101 at the recommended Phase 2 dose (“RP2D”). Updated clinical data indicate intratumoral TransCon TLR7/8 Agonist was generally well tolerated as monotherapy or when used in combination with pembrolizumab. In addition, monotherapy confirmed response in injected and non-injected tumors was observed, indicating abscopal effect and ability to induce systemic immune effects.
In November 2022, we announced new data (cutoff date of September 21, 2022) from the dose-escalation portion of transcendIT-101. All 23 of the patients enrolled in the dose escalation portion of the trial had advanced or metastatic solid tumors that had progressed on prior treatments, 9 in the monotherapy cohort (intratumoral TransCon TLR7/8 Agonist alone) and 14 in the combination therapy cohort (intratumoral TransCon TLR7/8 Agonist plus the check-point inhibitor pembrolizumab). Two dose levels were evaluated: 0.3 mg/lesion and 0.5 mg/lesion. The RP2D was declared at 0.5 mg/lesion for up to two lesions, which is being evaluated in four indication-specific cohorts.
TransCon IL-2 b/g for sustained systemic release
TransCon IL-2 b/g (onvapegleukin alfa) is an investigational long-acting prodrug designed to improve cancer immunotherapy through sustained release of an IL-2 variant that selectively activates IL-2 b/g, with minimal binding to IL-2Rα. The IL-Believe Trial, a Phase 1/2 clinical trial to evaluate the safety and efficacy of TransCon IL-2 b/g in locally advanced or metastatic solid tumors, alone or in combination with pembrolizumab or standard of care chemotherapy, has completed dose escalation and is enrolling patients in multiple indication-specific dose expansion cohorts, including platinum-resistant ovarian cancer (“PROC”), cervical cancer, melanoma, non-small cell lung cancer (“NSCLC”), and small cell lung cancer (“SCLC”) at the RP2D.
In September 2024, we announced initial data showing signs of clinical activity in heavily pre-treated patients with PROC treated with TransCon IL-2 β/γ in combination with chemotherapy in its ongoing Phase 1/2 IL-Believe Trial of TransCon IL-2 β/γ. Of the 18 patients (median age 64 years) included in the initial data, 14 were efficacy evaluable patients who had one or more post-baseline tumor assessment(s), plus an additional four who discontinued treatment before the first post-baseline tumor assessment due to disease progression or death. Anti-tumor clinical responses were observed in 29% (4/14) of the efficacy evaluable patients (two confirmed and two unconfirmed partial responses in patients who had received three to seven prior lines of treatment – including patients whose disease had previously progressed on mirvetuximab soravtansine-gynx), suggesting clinical activity in heavily pre-treated patients. The data suggest that TransCon IL-2 β/γ was generally well-tolerated: the most common treatment-emergent adverse events related to combination therapy with TransCon IL-2 β/γ plus chemotherapy were fatigue, thrombocytopenia, neutropenia, and anemia. Most TransCon IL-2 β/γ-related TEAEs were grade 1 or 2.
In June 2024, we reported interim results from our ongoing Phase 1/2 IL-Believe Trial of TransCon IL-2 b/g. Data included the first presentation of Phase 2 dose expansion Cohort 4 (TransCon IL-2 β⁄γ in combination with TransCon TLR7/8 Agonist) in post anti-PD-1 melanoma and new analyses of patients from dose escalation cohorts with prior disease progression on checkpoint inhibitors, along with biomarker studies correlating cytotoxic immune cell expansion and clinical benefit. As of the April 16, 2024, data cutoff, confirmed clinical responses were observed in 40% (two out of five) of efficacy-evaluable patients from Cohort 4, suggesting potential synergy of our two novel immunotherapy agents in patients who did not derive sufficient benefit from checkpoint inhibitors. Of efficacy-evaluable patients with prior disease progression on checkpoint inhibitors to date in the IL-Believe Trial, confirmed clinical responses (per RECIST v1.1) were observed in 45% (five out of eleven) administered TransCon IL-2 β/γ doses ≥80 μg/kg every 3 weeks, suggesting clinical benefit in treatment-resistant settings (monotherapy (n=4): 1 confirmed partial response (“PR”) in colorectal cancer; combination with pembrolizumab (n=2): 1 confirmed complete response and 1 confirmed PR in small-cell lung cancer; combination with TransCon TLR7/8 Agonist (n=5): 2 confirmed PRs in melanoma). In this trial, TransCon IL-2 β⁄γ alone or in combination with pembrolizumab or TransCon TLR7/8 Agonist was generally well tolerated with no new safety signals.
During the fourth quarter of 2023, the first patient was dosed with the combination of TransCon IL-2 b/g and TransCon TLR7/8 Agonist in the post PD-1 melanoma dose expansion cohort in the IL-Believe Trial.
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In October 2023, we announced new and updated data from the ongoing IL-Believe Trial. Forty-six patients were enrolled into dose escalation cohorts: 25 to monotherapy and 21 to combination therapy. As of the August 15, 2023, data cutoff, anti-tumor clinical responses were observed with TransCon IL-2 b/g monotherapy (colorectal cancer with PR) or in combination with pembrolizumab (small cell lung cancer, one with confirmed PR and one ongoing with unconfirmed complete response) in heavily pre-treated patients who previously progressed on checkpoint inhibitors. TransCon IL-2 b/g every three weeks was generally well-tolerated, with no meaningful effect on Tregs and eosinophils.
In September 2023, we announced completion of Phase 1 dose escalation in combination with pembrolizumab of the IL-Believe Trial with a total of 21 patients enrolled and RP2D determined at 120 µg/kg IV every three weeks. Twenty-one patients were enrolled.
In May 2023, we announced completion of the Phase 1 monotherapy dose escalation of the IL-Believe Trial with RP2D determined at 120 µg/kg IV every three weeks with 25 heavily pre-treated patients enrolled and a median of four prior lines of systemic therapies.
Other Development Plans
To further evaluate safety and anti-tumor efficacy of TransCon TLR7/8 Agonist and TransCon IL-2 b/g, we are also evaluating these product candidates as neoadjuvant therapy in the ongoing randomized Phase 2 BelieveIT-201 trial in resectable locally advanced head and neck squamous cell carcinoma.
Strategic Collaborations
We also engage in strategic collaborations to further leverage our TransCon technologies in certain geographies with market-leading biopharmaceutical companies. These collaborations aim to make promising treatment options available to more patients and to further monetize both our TransCon technologies and our internal product candidates, particularly into therapeutic areas where we believe a partner may have more expertise, capability, and capital. In addition, we may choose to pursue a collaboration to develop and market our internal, wholly owned product candidates in geographic markets outside our core focus areas of the United States and Europe.
Novo Nordisk
In November 2024, we entered into a research and development collaboration and license agreement with Novo Nordisk A/S (“Novo Nordisk”) pursuant to which we granted Novo Nordisk an exclusive worldwide license to the TransCon technology platform to develop, manufacture and commercialize Novo Nordisk proprietary products (including Semaglutide) in metabolic diseases (including obesity and type 2 diabetes) and a product-by-product exclusive license in cardiovascular diseases.
The agreement includes provisions requiring at least one TransCon Semaglutide product and at least one other TransCon technology-based product to be identified, developed and commercialized in metabolic diseases to maintain certain exclusivities in the field, with additional provisions for cardiovascular diseases. Under the terms of the agreement, Novo Nordisk also receives exclusive rights to expand any resulting metabolic disease products into other therapeutic areas. The lead program in the collaboration is a once-monthly TransCon Semaglutide product candidate that will initially target obesity and type 2 diabetes.
Under the agreement, we have the potential to receive total payments of up to $285 million in upfront, development and regulatory milestone payments for the lead program. In addition, we have the potential to receive sales-based milestone payments and tiered royalties on global net sales. The $285 million includes an upfront fee of $100 million for the exclusive license. For each additional metabolic or cardiovascular disease product candidate, we will be eligible to receive payments of up to $77.5 million in development and regulatory milestone payments. In addition, we have the potential to receive sales-based milestone payments and tiered royalties on global net sales. Novo Nordisk agreed to pay royalties for each potential licensed product developed under the agreement that are an escalating tiered, mid-single digit percentage of the annual net sales of such licensed product and are subject to reduction due to patent valid claim expiration, biosimilar product market share, payment made under certain licenses for third party intellectual property and Inflation Reduction Act price negotiations.
Under the agreement, we will conduct certain pre-agreed early research and development of TransCon product candidates under the collaboration and the Company is eligible to receive cost reimbursement from Novo Nordisk for its performance of such research and development activities under the agreement with respect to such TransCon product candidates. Novo Nordisk will be responsible for any other non-clinical and clinical development, regulatory, commercial manufacturing, and commercialization of such TransCon product candidates, and all costs associated with such activities.
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Subject to the terms of the agreement, we granted Novo Nordisk an exclusive, worldwide, royalty-bearing license, with the right to grant sublicenses, to use its proprietary TransCon technology platform to develop, manufacture and commercialize Novo Nordisk proprietary products in metabolic diseases (including obesity and type 2 diabetes) and a product-by-product exclusive license in cardiovascular diseases. Additionally, we have granted Novo Nordisk an exclusive, worldwide, royalty-bearing license, with the right to grant sublicenses, to use its proprietary TransCon technology platform to develop, manufacture and commercialize GLP-1 receptor products using the TransCon technology for all indications, except for (i) certain pre-agreed rare endocrine indications, (ii) all indications in respect of the eye and adnexa and (iii) all indications in respect of oncology.
Until expiry of the last royalty term and for one-year thereafter, the we will not be permitted to research, develop, manufacture, commercialize, or otherwise exploit outside of the collaboration, any GLP-1 receptor product or any other licensed products that have been subject to the collaboration. We are also not permitted to undertake any research, development, manufacture, commercialization, or other exploitation of products outside of the collaboration in the metabolic field until expiry of the last royalty term of any licensed products that have been subject to the collaboration in metabolic diseases.
Unless earlier terminated, the agreement has a royalty term that continues, on a per licensed product and per country basis, until the later of (i) the expiration of the last valid patent claim for any of our patents, joint improvement patents, licensed product patents as well as any improvements made by Novo Nordisk covering the licensed product’s dosage regimen or target product profile, or (ii) 11 years after the first commercial sale of such licensed product in such country.
Novo Nordisk has the right to terminate the agreement without cause in its entirety or on a per licensed product basis. We have the right to terminate the agreement in its entirety in case Novo Nordisk brings patent challenges with respect to our patents. The agreement may also be terminated by either party based on an uncured material breach by the other party or the bankruptcy of the other party.
Upon termination of the agreement due to Novo Nordisk’s default, some or all of the licenses granted by us to Novo Nordisk to develop, manufacture and commercialize any of the licensed products will automatically terminate.
Upon termination of the agreement due to certain defaults by Ascendis, Novo Nordisk may choose to either (i) have the license granted by us to Novo Nordisk to develop, manufacture and commercialize licensed products terminate in its entirety or on a product-by-product basis; or (ii) continue with respect to the affected licensed product at a reduced payment rate.
The closing of this transaction with Novo Nordisk is subject to receipt of applicable regulatory approvals and the parties are seeking to close before the end of 2024.
Teijin Limited
In November 2023, we announced that we entered into an exclusive license agreement with Teijin Limited for the further development and commercialization of TransCon hGH, TransCon PTH, and TransCon CNP for endocrinology rare disease in Japan. Under the terms of the agreement with Teijin Limited, we received an upfront payment of $70 million, with additional development and regulatory milestones of up to $175 million, transfer pricing and commercial milestones. In addition, we are eligible to receive royalties on net sales in Japan, of up to a mid-20’s percentage, varying by product.
Strategic Investments
VISEN Pharmaceuticals
In November 2018, we announced the formation of VISEN, a company established to develop and commercialize our endocrinology rare disease therapies in the People’s Republic of China, Hong Kong, Macau, and Taiwan (“Greater China”). In connection with the formation of VISEN, we granted VISEN exclusive rights to develop and commercialize certain product candidates based on our proprietary TransCon technologies, including TransCon hGH, TransCon PTH, and TransCon CNP, in Greater China for use in all human indications, subject to certain exceptions. As consideration for the rights granted to VISEN, we received 50% ownership in the outstanding shares of VISEN and concurrently with the rights we granted to VISEN, entities affiliated with Vivo Capital and Sofinnova Ventures purchased shares in VISEN for an aggregate purchase price of $40 million in cash. In January 2021, we invested additional $12.5 million in VISEN as part of VISEN’s $150 million Series B financing. Following the Series B financing, we retained 43.93% of VISEN’s issued and outstanding shares.
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In August 2024, VISEN announced topline data from the 26-week randomized, double-blind, placebo-controlled portion of the Phase 3 PaTHway China Trial of Palopegteriparatide (TransCon PTH) in adults with chronic hypoparathyroidism. A statistically significantly higher proportion of patients treated with palopegteriparatide achieved the primary multi-component endpoint compared to placebo (p-value <0.0001). Palopegteriparatide was generally safe and well-tolerated, with no discontinuations related to study drug. Results were consistent with those announced by Ascendis Pharma for its palopegteriparatide Phase 3 trial.
In March 2024, VISEN announced that the BLA for lonapegsomatropin (TransCon hGH) was accepted by the China National Medical Products Administration. Lonapegsomatropin is the first once-weekly administrated growth hormone approved by both the FDA and EMA for the treatment of pediatric GHD.
In November 2023, VISEN announced topline results from the Phase 2 ACcomplisH China Trial in children with achondroplasia aged 2 to 10 years. The trial met its primary objectives, demonstrating that TransCon CNP at 100 µg/kg/week was superior to placebo on the primary efficacy endpoint of AGV at 52 weeks (p=0.018).
In November 2022, VISEN announced data from its pivotal Phase 3 study of TransCon hGH in children with GHD in China. The trial achieved its primary endpoint; patients treated with TransCon hGH demonstrated greater annualized height velocity at 52-weeks (p=0.0010) compared to patients treated with daily growth hormone with comparable safety and tolerability to daily growth hormone.
Market Opportunity in China
China is the second largest pharmaceutical market in the world after the United States and represents one of the fastest growing pharmaceutical markets worldwide. In recent years, the Chinese government has initiated a number of regulatory reforms that are expected to accelerate drug development, as well as drive growth and demand for new therapeutics in China. In addition to joining an international organization that standardizes regulations for clinical development, the National Medical Products Administration has introduced initiatives such as fast track review for drugs for unmet medical needs and adopted new rules that streamline the drug approval process in China for global companies.
The purpose of our investment in VISEN is to support our strategy to extend our endocrinology rare disease portfolio globally and establish a presence in China in partnership with collaborators who have significant experience and knowledge of the biopharmaceutical opportunity in China.
Rights Agreements
Under three exclusive license agreements, each effective November 7, 2018, and as amended January 4, 2021, between the Company and VISEN (collectively, the “Rights Agreements”), VISEN must use diligent efforts to develop and commercialize licensed products in Greater China. Additionally, we and VISEN will conduct certain research and development activities allocated to the respective party under a research and technical development plan, and VISEN will reimburse us for costs of conducting such activities, including costs of our personnel committed to performing such activities in Greater China.
We entered into a clinical supply agreement with VISEN in 2018 to provide product supply for use in conducting clinical trials in Greater China. Additionally, during 2023, we entered into a commercial supply agreement governing commercial supply of licensed product (TransCon hGH) to VISEN on the terms and conditions set forth in the Rights Agreements.
Under the Rights Agreements, we agreed not to research, develop, or commercialize competing products in Greater China, and VISEN agreed not to grant certain rights under its interest in any inventions or intellectual property arising out of the activities conducted under the Rights Agreements to third-parties, in each case, under the terms and conditions specified in the Rights Agreements. We will have the right to exploit inventions and intellectual property arising out of the activities conducted under the Rights Agreements outside of Greater China. Additionally, we granted VISEN a right of first negotiation to develop and commercialize certain of our endocrinology products in Greater China.
The Rights Agreements continue in effect for as long as a valid claim of a licensed patent exists in Greater China. VISEN may terminate a Rights Agreement for convenience, for uncured material breach by us of a Rights Agreement and for our bankruptcy or insolvency-related events. We may terminate a Rights Agreement for certain specified material breaches thereof by VISEN, in the event VISEN undergoes a change of control in favor of a competitor, if VISEN challenges the validity of any of the licensed patents and for VISEN’s bankruptcy or insolvency-related events.
22
Amended and Restated Shareholders Agreement
In connection with the Company’s investment in VISEN, on January 8, 2021, the Company entered into an Amended and Restated Shareholders Agreement (the “Amended Shareholders Agreement”), amending and restating the Shareholders Agreement dated November 7, 2018, between the Company and the parties set forth therein (the “Shareholders Agreement”). In addition to rights previously granted under the Shareholders Agreement, under the Amended Shareholders Agreement, the Company has the right to designate two individuals for election to the board of directors of VISEN, which individuals are Jan Møller Mikkelsen and Michael Wolff Jensen. In addition, VISEN has agreed that certain specified events (including certain liquidation events) shall require the approval of (i) shareholders of VISEN holding at least 50% of VISEN’s Series B preferred shares, (ii) shareholders of VISEN holding at least 60% of VISEN’s Series A preferred shares and/or (iii) certain members of VISEN’s board of directors. The Amended Shareholders Agreement can be terminated by written agreement among the holders of at least 60% of VISEN’s Series A preferred shares and at least 50% of VISEN’s Series B preferred shares.
Eyconis
In January 2024, we announced the formation and launch with Frazier Life Sciences of Eyconis, Inc., a separate company created to develop, manufacture, and commercialize TransCon ophthalmology assets globally, together with a $150 million commitment from an investor syndicate that includes Frazier, RA Capital Management, venBio, and HealthQuest Capital.
We have granted Eyconis exclusive rights to develop and commercialize TransCon ophthalmology products globally and received an equity position in the newly formed company. In addition, we will be eligible to receive development, regulatory, and sales milestone payments, plus single digit royalties on global net sales of commercialized products, if any. Eyconis will initially be based in Redwood City, California, and certain employees of Ascendis have joined the newly formed company.
23
Results of Operations
Financial Highlights (unaudited)
|
|
Three Months Ended |
|
|
Nine Months Ended |
|
||||||||||
|
|
2024 |
|
|
2023 |
|
|
2024 |
|
|
2023 |
|
||||
|
|
(EUR’000) |
|
|||||||||||||
Revenue |
|
|
57,833 |
|
|
|
48,034 |
|
|
|
189,725 |
|
|
|
129,016 |
|
Gross profit |
|
|
46,632 |
|
|
|
40,646 |
|
|
|
159,490 |
|
|
|
104,078 |
|
Operating expenses (1) |
|
|
143,375 |
|
|
|
175,053 |
|
|
|
438,636 |
|
|
|
523,008 |
|
Operating profit/(loss) |
|
|
(96,743 |
) |
|
|
(134,407 |
) |
|
|
(279,146 |
) |
|
|
(418,930 |
) |
Net profit/(loss) for the period |
|
|
(99,198 |
) |
|
|
(162,223 |
) |
|
|
(339,615 |
) |
|
|
(394,569 |
) |
Cash flows from/(used in) operating activities |
|
|
(56,131 |
) |
|
|
(124,719 |
) |
|
|
(219,021 |
) |
|
|
(424,891 |
) |
Compared to the three and nine months ended September 30, 2023, revenue for the three and nine months ended September 30, 2024 primarily benefited from continued demand growth for SKYTROFA® (lonapegsomatropin-tcgd) in the U.S. which was offset by higher sales deductions, non-cash license revenue related to our exclusive license agreement with Eyconis in January 2024, and launch of YORVIPATH® (palopegteriparatide) in Europe. For the nine months ended September 30, 2024, this increase was partly offset by a negative adjustment to estimates and assumptions for sales deductions related to sale of SKYTROFA, which were attributable to periods prior to January 1, 2024.
Operating loss for the three and nine months ended September 30, 2024, represented a decrease of €37.7 million and €139.8 million, compared to the same period last year, primarily attributable to lower operating expenses, higher revenue from commercial sales and from non-cash license revenue related to our exclusive license agreement with Eyconis in January 2024.
We had a net loss of €339.6 million for the nine months ended September 30, 2024, compared to a net loss of €394.6 million for the same period last year. Total equity presented a negative balance of €97.3 million as of September 30, 2024, compared to a negative balance of €145.7 million as of December 31, 2023.
Further details about our results of operations and cash flows are described in the following sections.
Comparison of the Three and Nine Months Ended September 30, 2024 and 2023 (unaudited)
Revenue
Revenue for the three and nine months ended September 30, 2024 were €57.8 million and €189.7 million, representing an increase of €9.8 million and €60.7 million, compared to the same period last year. The increase for the nine months ended September 30, 2024 was primarily attributable to continued demand growth of SKYTROFA which was offset by higher sales deductions due to the shift to broader market access compared to the prior periods, recognition of non-cash license revenue of €26.5 million related to our exclusive license agreement with Eyconis in January 2024, and €15.1 million from YORVIPATH following commercial launch in the first quarter of 2024. The increase for the three months ended September 30, 2024 was primarily attributable to €8.5 million from YORVIPATH.
In addition, revenue for the nine months ended September 30, 2024, was negatively impacted by an adjustment to estimates and assumptions for sales deductions of €9.3 million, which were attributable to periods prior to January 1, 2024. The adjustment was primarily attributable to a different payer and rebate mix than anticipated, and on which provisions for prior periods were based.
The development in quarterly revenue from sale of commercial products was as follows:
|
|
Three Months Ended, |
||||||||
|
|
September 30, 2023 |
|
December 31, 2023 |
|
March 31, 2024 |
|
June 30, 2024 |
|
September 30, 2024 |
|
|
(EUR’000) |
||||||||
Revenue from commercial products |
|
46,968 |
|
64,249 |
|
66,499 |
|
31,389 |
|
55,710 |
Cost of Sales
Cost of sales for the three and nine months ended September 30, 2024 was €11.2 million and €30.2 million, representing an increase of €3.8 million and €5.3 million compared to the same period last year. This increase was primarily attributable to higher volume of commercial sales and, for the nine months ended September 30, 2024 partly offset by lower costs associated with delivering of services under our license and collaboration agreements compared to the same period last year.
24
Research and Development Costs
The following table specifies external project costs on the development pipeline and other research and development costs.
|
|
Three Months Ended |
|
Nine Months Ended |
||||
|
|
2024 |
|
2023 |
|
2024 |
|
2023 |
|
|
(EUR’000) |
|
(EUR’000) |
||||
External project costs |
|
|
|
|
|
|
|
|
TransCon hGH |
|
11,328 |
|
20,892 |
|
35,634 |
|
51,782 |
TransCon PTH |
|
2,141 |
|
10,600 |
|
1,699 |
|
33,214 |
TransCon CNP |
|
13,925 |
|
18,627 |
|
45,184 |
|
43,045 |
TransCon IL-2 ß/γ |
|
6,734 |
|
10,279 |
|
21,672 |
|
30,006 |
TransCon TLR7/8 Agonist |
|
3,242 |
|
7,843 |
|
8,441 |
|
28,417 |
Ophthalmology |
|
— |
|
5,543 |
|
— |
|
10,302 |
Other project costs |
|
(885) |
|
129 |
|
1,075 |
|
673 |
Total external project costs |
|
36,485 |
|
73,913 |
|
113,705 |
|
197,439 |
Other research and development costs |
|
|
|
|
|
|
|
|
Employee costs |
|
32,038 |
|
30,483 |
|
96,817 |
|
99,065 |
Other costs |
|
3,240 |
|
4,069 |
|
11,758 |
|
17,272 |
Depreciation |
|
1,781 |
|
2,974 |
|
5,428 |
|
8,797 |
Total other research and development costs |
|
37,059 |
|
37,526 |
|
114,003 |
|
125,134 |
Total research and development costs |
|
73,544 |
|
111,439 |
|
227,708 |
|
322,573 |
R&D costs for the three and nine months ended September 30, 2024 were €73.5 million and €227.7 million, representing a decrease of €37.9 million and €94.9 million compared to the same period last year. This decrease was primarily due to:
The development in quarterly external project costs was as follows:
|
|
Three Months Ended, |
|
|||||||||||||||||
|
|
September 30, 2023 |
|
|
December 31, 2023 |
|
|
March 31, 2024 |
|
|
June 30, 2024 |
|
|
September 30, 2024 |
|
|||||
|
|
(EUR’000) |
|
|||||||||||||||||
External project costs |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
TransCon hGH |
|
|
20,892 |
|
|
|
12,197 |
|
|
|
11,816 |
|
|
|
12,491 |
|
|
|
11,328 |
|
TransCon PTH |
|
|
10,600 |
|
|
|
7,366 |
|
|
|
(6,319 |
) |
|
|
5,876 |
|
|
|
2,141 |
|
TransCon CNP |
|
|
18,627 |
|
|
|
15,570 |
|
|
|
15,744 |
|
|
|
15,515 |
|
|
|
13,925 |
|
TransCon IL-2 b/g |
|
|
10,279 |
|
|
|
1,987 |
|
|
|
6,964 |
|
|
|
7,973 |
|
|
|
6,734 |
|
TransCon TLR7/8 Agonist |
|
|
7,843 |
|
|
|
5,066 |
|
|
|
2,910 |
|
|
|
2,290 |
|
|
|
3,242 |
|
Ophthalmology |
|
|
5,543 |
|
|
|
6,419 |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
Other project costs |
|
|
129 |
|
|
|
353 |
|
|
|
1,224 |
|
|
|
736 |
|
|
|
(885 |
) |
Total external project costs |
|
|
73,913 |
|
|
|
48,958 |
|
|
|
32,339 |
|
|
|
44,881 |
|
|
|
36,485 |
|
25
Selling, General and Administrative Expenses
The following table specifies selling, general and administrative expenses:
|
|
Three Months Ended |
|
|
Nine Months Ended |
|
||||||||||
|
|
2024 |
|
|
2023 |
|
|
2024 |
|
|
2023 |
|
||||
|
|
(EUR’000) |
|
|
(EUR’000) |
|
||||||||||
Selling, general, and administrative expenses |
|
|
|
|
|
|
|
|
|
|
|
|
||||
Employee costs |
|
|
35,044 |
|
|
|
28,381 |
|
|
|
103,995 |
|
|
|
86,079 |
|
Other costs |
|
|
33,085 |
|
|
|
34,132 |
|
|
|
101,769 |
|
|
|
110,583 |
|
Depreciation |
|
|
1,702 |
|
|
|
1,101 |
|
|
|
5,164 |
|
|
|
3,773 |
|
Total selling, general, and administrative expenses |
|
|
69,831 |
|
|
|
63,614 |
|
|
|
210,928 |
|
|
|
200,435 |
|
Selling, general, and administrative (“SG&A”) expenses for the three and nine months ended September 30, 2024 were €69.8 million and €210.9 million, representing an increase of €6.2 million and €10.5 million compared to the same period last year. This increase was primarily due to higher employee costs, including the impact from commercial expansion. Other costs decreased primarily due to lower pre-launch and other administrative costs, partly offset by higher costs related to the European launch activities.
The development in quarterly SG&A expenses was as follows:
|
|
Three Months Ended, |
|
|||||||||||||||||
|
|
September 30, 2023 |
|
|
December 31, 2023 |
|
|
March 31, 2024 |
|
|
June 30, 2024 |
|
|
September 30, 2024 |
|
|||||
|
|
(EUR’000) |
|
|||||||||||||||||
Selling, general, and administrative expenses |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
Employee costs |
|
|
28,381 |
|
|
|
29,627 |
|
|
|
33,543 |
|
|
|
35,409 |
|
|
|
35,044 |
|
Other costs |
|
|
34,132 |
|
|
|
32,016 |
|
|
|
31,795 |
|
|
|
36,886 |
|
|
|
33,085 |
|
Depreciation |
|
|
1,101 |
|
|
|
2,332 |
|
|
|
1,445 |
|
|
|
2,017 |
|
|
|
1,702 |
|
Total selling, general and administrative expenses |
|
|
63,614 |
|
|
|
63,975 |
|
|
|
66,783 |
|
|
|
74,312 |
|
|
|
69,831 |
|
26
Finance Income and Finance Expenses
The following table specifies the result of finance income and expenses, further disaggregated into cash and non-cash items:
|
|
Three Months Ended |
|
|
Nine Months Ended |
|
||||||||||
|
|
2024 |
|
|
2023 |
|
|
2024 |
|
|
2023 |
|
||||
|
|
(EUR’000) |
|
|||||||||||||
Net finance income/(expenses) |
|
|
|
|
|
|
|
|
|
|
|
|
||||
Finance income |
|
|
28,279 |
|
|
|
4,142 |
|
|
|
29,262 |
|
|
|
76,985 |
|
Finance expenses |
|
|
(25,347 |
) |
|
|
(24,519 |
) |
|
|
(70,488 |
) |
|
|
(35,640 |
) |
Total net finance income/(expenses) |
|
|
2,932 |
|
|
|
(20,377 |
) |
|
|
(41,226 |
) |
|
|
41,345 |
|
Specified in cash and non-cash items |
|
|
|
|
|
|
|
|
|
|
|
|
||||
Cash items |
|
|
|
|
|
|
|
|
|
|
|
|
||||
Finance income received |
|
|
2,658 |
|
|
|
4,174 |
|
|
|
8,923 |
|
|
|
12,577 |
|
Finance expenses paid |
|
|
(849 |
) |
|
|
(886 |
) |
|
|
(8,563 |
) |
|
|
(8,632 |
) |
Non-cash items |
|
|
|
|
|
|
|
|
|
|
|
|
||||
Remeasurement gain/(loss) of financial liabilities |
|
|
(9,287 |
) |
|
|
(6,968 |
) |
|
|
(16,907 |
) |
|
|
64,597 |
|
Currency gain/(loss) |
|
|
25,621 |
|
|
|
(6,475 |
) |
|
|
12,210 |
|
|
|
(5,912 |
) |
Amortization charges, accruals, and other items |
|
|
(15,210 |
) |
|
|
(10,222 |
) |
|
|
(36,889 |
) |
|
|
(21,285 |
) |
Total net finance income/(expenses) |
|
|
2,932 |
|
|
|
(20,377 |
) |
|
|
(41,226 |
) |
|
|
41,345 |
|
The development in non-cash items was primarily due to remeasurement of financial liabilities, which influenced especially the nine months ended September 30, 2024. The increase in amortization charges, accruals, and other items primarily relates to amortization charges and interests on convertible notes and royalty funding liabilities, which we entered into in September 2023 and September 2024. In addition, the development in currency gain/(loss) was primarily driven by conversion of U.S. dollar denominated monetary positions into Euro, primarily cash and cash equivalents, convertible notes and royalty funding liabilities.
27
Liquidity and Capital Resources
Our liquidity and capital resources comprise cash and cash equivalents, which as of September 30, 2024, amounted to €625.5 million.
Our expenditures primarily relate to continued development of our endocrinology rare disease and oncology therapeutic areas, the commercialization of SKYTROFA and YORVIPATH, and expenses made in anticipation of potential future product launches. We manage our liquidity risk by maintaining adequate cash reserves and banking facilities in line with our cash forecasts. We monitor the risk of a shortage of funds through liquidity planning tools, to ensure sufficient funds are available to settle liabilities as they become due.
As of September 30, 2024, the unaudited condensed consolidated interim statements of financial position presented a negative balance of equity of €97.3 million. Under Danish corporate law, as Ascendis Pharma A/S, the parent company of the Company holds a positive balance of equity, the Company is currently not subject to legal or regulatory requirements to re-establish the balance of equity. There is no direct impact from the negative balance of equity to the liquidity and capital resources.
Based on our current operating plan, we believe that our existing capital resources as of September 30, 2024, will be sufficient to meet our projected cash requirements for at least twelve months from the date of this report. However, our operating plan may change as a result of many factors currently unknown to us, and we may need to seek additional funds sooner than planned.
Historically, we have funded our operations primarily through the issuance of preference shares, ordinary shares (including public offerings and exercise of warrants), convertible debt securities, payments to us made under collaboration agreements, and our royalty funding agreement. Including our initial public offering, since February 2015, we have completed public offerings of American Depositary Shares (“ADSs”), latest in September 2024, with net proceeds of $2,580.2 million (or €2.259.0 million at the time of the offerings).
In September 2024, we entered into a $150.0 million capped synthetic royalty funding agreement (the “Royalty Pharma Yorvipath Agreement”) with Royalty Pharma (the “Purchaser”). Under the terms of the Royalty Pharma Yorvipath Agreement, in exchange for Purchaser’s payment of a cash purchase price of $150.0 million at closing (the “Yorvipath Purchase Price”), we have agreed to sell to the Purchaser its right to receive payment in full of 3% on net revenue from sales of YORVIPATH in the U.S. (the “Yorvipath Revenue Payments”). The Yorvipath Revenue Payments to the Purchaser will cease upon reaching a multiple of the Yorvipath Purchase Amount of 2.0 times, or 1.65 times if the Purchaser receives Yorvipath Revenue Payments in that amount by December 31, 2029. The Royalty Pharma Yorvipath Agreement includes a buy-out option under various terms and conditions.
In September 2023, we entered into a $150.0 million capped synthetic royalty funding agreement (the “Royalty Pharma Skytrofa Agreement”) with the Purchaser. Under the terms of the Royalty Pharma Skytrofa Agreement, in exchange for the Purchaser’s payment of a cash purchase price of $150.0 million at closing (the “Skytrofa Purchase Price”), we have agreed to sell to the Purchaser its right to receive payment in full of 9.15% on net revenue from sales of SKYTROFA revenue in the U.S., beginning on January 1, 2025 (the “Skytrofa Revenue Payments”). The Skytrofa Revenue Payments to the Purchaser will cease upon reaching a multiple of the Skytrofa Purchase Price of 1.925 times, or 1.65 times if the Purchaser receives Skytrofa Revenue Payments in that amount by December 31, 2031. The Royalty Pharma Skytrofa Agreement includes a buy-out option under various terms and conditions.
In March 2022, we issued an aggregate principal amount of $575.0 million of fixed rate 2.25% convertible notes. The coupon interest is payable semi-annually. Unless earlier converted or redeemed, the convertible notes will mature on April 1, 2028. We used $116.7 million (€105.3 million) of the net proceeds from the offering in March 2022 to repurchase 1,000,000 ADSs representing our ordinary shares. The holding of treasury shares is disclosed in Note 9, “Treasury Shares.”
Further details regarding our borrowings are provided in Note 10, “Financial Assets and Liabilities.”
For additional description of our cash requirements, public offerings, expense structure and commitments, refer to “Item 5B. Liquidity and Capital Resources,” set forth in our Annual Report on Form 20-F filed with the Securities and Exchange Commission on February 7, 2024.
Our future funding requirements will depend on many factors, including, but not limited to:
28
Additional funds may not be available if we need them or on terms that are acceptable to us, or at all. If adequate funds are not available to us on a timely basis, we may be required to delay, limit, scale back or cease our research and development and commercialization activities.
The following table summarizes our cash flows for the nine months ended September 30, 2024 and 2023:
|
|
Nine Months Ended |
|
|||||||||
|
|
2024 |
|
|
2023 |
|
|
Change |
|
|||
|
|
(EUR’000) |
|
|||||||||
Cash flows from/(used in) |
|
|
|
|
|
|
|
|
|
|||
Operating activities |
|
|
(219,021 |
) |
|
|
(424,891 |
) |
|
|
205,870 |
|
Investing activities |
|
|
7,260 |
|
|
|
279,823 |
|
|
|
(272,563 |
) |
Financing activities |
|
|
443,842 |
|
|
|
140,347 |
|
|
|
303,495 |
|
Net increase/(decrease) in cash and cash equivalents |
|
|
232,081 |
|
|
|
(4,721 |
) |
|
|
236,802 |
|
Cash Flows from / (used in) Operating Activities
Cash flows used in operating activities for the nine months ended September 30, 2024, were €219.0 million, representing a decrease of €205.9 million compared to the same period last year. This improvement is primarily related to higher commercial revenue and reduced operating expenditures, and to further adjustment for changes to non-operating financial income and expenses, taxes and non-cash items of total €127.2 million. In addition, the change in cash flows from operations was positively impacted by working capital balances with €78.7 million.
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Cash Flows from / (used in) Investing Activities
Cash flows from investing activities for the nine months ended September 30, 2024, were €7.3 million, representing a decrease of €272.6 million compared to the same period last year. This decrease was primarily attributable to €275.0 million higher net settlements of marketable securities in 2023 in line with our liquidity management strategy.
Cash Flows from / (used in) Financing Activities
Cash flows from financing activities for the nine months ended September 30, 2024 were €443.8 million, representing an increase of €303.5 million compared to the same period last year. This increase was primarily attributable to our follow-on public offering of ADSs completed in September 2024 with net proceeds of €290.6 million and increased warrant exercise activity of €19.2 million. In addition, and similarly to the same period last year, we entered into a $150.0 million capped synthetic royalty funding agreement, with net proceeds of €134.2 million, compared with €139.8 million for the same period last year.
Off-Balance Sheet Arrangements
We have not entered into any off-balance sheet arrangements or any holdings in variable interest entities.
Qualitative Disclosures about Market Risk
Our activities expose us to financial risks of changes in foreign currency exchange rates, inflation rates and interest rates. We do not enter into derivative financial instruments to manage our exposure to such risks. Further, we are exposed to credit risk, equity risk and liquidity risk. For a description of our exposure to liquidity risks, including risks associated with the royalty funding liabilities and processes for managing these risks, please refer to “Liquidity and Capital Resources,” set forth above, and maturity analysis for non-derivative financial liabilities provided in Note 10, “Financial Assets and Liabilities.”
Foreign Currency Risk
We are exposed to foreign exchange risk arising from various currency exposures, primarily with respect to the U.S. Dollar. While we generate revenue in Euro, a significant portion of our revenue is denominated in U.S. Dollars. Similarly, a significant portion of our operating expenses are denominated in U.S. Dollars. In addition, our outstanding convertible notes and royalty funding liabilities are denominated in U.S. Dollars. We seek to minimize our exchange rate risk by maintaining cash positions in the currencies in which we expect to incur the majority of our future expenses and we make payments from those positions.
Interest Rate Risk
Outstanding convertible notes comprise a 2.25% coupon fixed rate structure. In addition, the interest rate on lease liabilities is fixed at the lease commencement date. Future indebtedness, including those related to lease arrangements, if any, may be subject to higher interest rates. In addition, future interest income from interest-bearing bank deposits may fall short of expectations due to changes in interest rates.
Derivative liabilities are measured at fair value through profit or loss. Accordingly, since the fair value is exposed from the development in interest rates, the profit or loss is exposed to volatility from such development.
Inflation Risk
Inflation affects us as our vendors may pass on any increased costs to us and accordingly increase our R&D costs, SG&A expenses and cost of manufacturing. We do not believe that inflation had a material impact on our results of operation for the three and nine months ended September 30, 2024.
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Credit Risk
We have adopted an investment policy with the primary purpose of preserving capital, fulfilling our liquidity needs and diversifying the risks associated with cash, cash equivalents and marketable securities. Our investment policy establishes minimum ratings for institutions with which we hold cash, cash equivalents and marketable securities, as well as rating and concentration limits for marketable securities held. All material counterparties are considered creditworthy. While the concentration of credit risk may be significant, the credit risk for each individual counterpart is considered to be low. Our exposure to credit risk primarily relates to cash and cash equivalents. The credit risk on our bank deposits is limited because the counterparties holding significant deposits are banks with high credit-ratings (minimum A3/A-) assigned by international credit-rating agencies.
We maintain the majority of our cash and cash equivalents in accounts with major financial institutions, and our deposits at these institutions exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our business and financial position. The banks are reviewed on a regular basis and deposits may be transferred during the year to mitigate credit risk.
In order to mitigate the concentration of credit risks on bank deposits and to preserve capital, a portion of the bank deposits may be placed into marketable securities. Our investment policy, approved by the Board, only allows investment in marketable securities having investment grade credit-ratings, assigned by international credit-rating agencies. As of June 30, 2024, we do not hold marketable securities.
On each reporting date, we consider the risk of expected credit loss on bank deposits and marketable securities, if any, including the hypothetical impact arising from the probability of default, which is considered in conjunction with the expected loss caused by default by banks or securities with similar credit-ratings and attributes. In line with previous periods, this assessment did not reveal a material impairment loss, and accordingly no provision for expected credit loss has been recognized.
Equity Risk
We are exposed from the development in our share price, when remeasuring derivative liabilities at fair value.
Derivative liabilities relate to the foreign currency conversion option embedded in the convertible notes and are measured at fair value through profit or loss. Fair value cannot be measured based on quoted prices in active markets or other observable inputs, and accordingly, derivative liabilities are measured by using the Black-Scholes option pricing model, where the pricing is exposed from changes in our share price. Sensitivity analysis over derivative liabilities is disclosed in Note 10, “Financial Assets and Liabilities.”
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